5-chloro-2-difluoromethoxyphenyl pyrazolopyrimidine compounds,compositions and methods of use thereof

A compound of Formula (00A):

• and stereoisomers and salts thereof, wherein:
• R00 is H or CH3;
• R01 is H or NH2;
• R0 is H or NH2;
• and Ring Q is either (i) or (ii):
• wherein:
• t1 and t2 are each independently 0 or 1;
• XA and XB are independently selected from the group consisting of H, C1-C6 alkyl, C2-C4 alkenyl, —NRaRb, C2-C5 alkynyl, 3-6-membered cycloalkyl, 6-10 membered aryl, 3-11 membered heterocycloalkyl, 5-6 membered heterocycloalkenyl, and 5-10 membered heteroaryl;
• wherein when either of XA and XB are independently C1-C6 alkyl, C2-C4 alkenyl, C2-C5 alkynyl, 3-6-membered cycloalkyl, 6-10 membered aryl, 3-11 membered heterocycloalkyl, 5-6 membered heterocycloalkenyl, and 5-10 membered heteroaryl, each of XA and XB is independently optionally substituted by Y1, wherein Y1 is selected from:
• (a) C1-C6 alkyl optionally substituted by T1, wherein T1 is selected from the group consisting of OH, halo, CN, imino, 3-6 membered cycloalkyl, 3-11 membered heterocycloalkyl, 3-11 membered heterocycloalkenyl, 5-10 membered heteroaryl, —O—(C1-C6 alkyl), C(O)OH, oxetan-3-ylmethyl, —C(O)O—(C1-C6 alkyl), —S—(C1-C6 alkyl), —SO2—(C1-C6 alkyl), —NRaRb, —N(+)RaRbRc wherein Rc is methyl, —C(O)NRaRb, -(2-oxoindolin-1-yl), —OC(O)-3-6 membered cycloalkyl, and phenyl, wherein each alkyl, cycloalkyl, heterocycloalkyl, heterocycloalkenyl, heteroaryl, and phenyl of T1 is optionally substituted by OH, —C(O)O—(C1-C6 alkyl), C1-C6 alkyl, halo, CN, oxo, —(C1-C6 alkyl)CONRaRb, —NRaRb, phenyl, or —O—(C1-C6 alkyl) optionally substituted by OH;
• (b) 3-11 membered heterocycloalkyl, —(C1-C6 alkylene)-3-11 membered heterocycloalkyl, —C(O)-3-11 membered heterocycloalkyl, —(C1-C6 alkylene)C(O)-3-11 membered heterocycloalkyl, or —OC(O)-4-6 membered heterocycloalkyl;
• wherein the heterocycloalkyl is optionally substituted by OH, halo, CN, C1-C6 alkyl, —(C1-C6 alkylene)-CF3, oxo, —C(O)—(C1-C6 alkyl), —C(O)O—(C1-C6 alkyl), —C(O)O—(C1-C6 alkylene)-phenyl, —SO2—(C1-C6 alkyl), —C(O)NRaRb, —NRaRb, —(C1-C6 alkylene)-phenyl, or —C(O)-4-6 membered heterocycloalkyl optionally substituted by —NRaRb;
• (c) N(+)(AA)3, wherein each AA is independently C1-C6 alkyl optionally substituted by phenyl;
• (d) 3-6 membered cycloalkyl optionally substituted by OH, halo, NRaRb, or CN;
• (e) CN, halo, or oxo;
• (f) —C(O)—(C1-C6 alkyl), —C(O)OH, —C(O)O—(C1-C6 alkylene)-phenyl, —SO2—(C1-C6 alkyl), —C(O)NRaRb, or —C(O)-4-6 membered heterocycloalkyl optionally substituted by —(C1-C6 alkyl) or —NRaRb, or —C(O)O—(C1-C6 alkyl) optionally substituted by OH, NRaRb, or 3-11 membered heterocycloalkyl wherein said heterocycloalkyl is optionally substituted by C1-C6 alkyl;
• (g) OH, —O-phenyl, or —O—(C1-C6 alkyl), wherein the alkyl is optionally substituted by OH or —NRaRb;
• (h) phenyl optionally substituted by OH, halo, C1-C6 alkyl, CF3, or CN;
• (i) 5-6 membered heteroaryl optionally substituted by OH, halo, C1-C6 alkyl, CF3, CN, or 3-11 membered heterocycloalkyl optionally substituted by C1-C6 alkyl or 3-11 membered heterocycloalkyl;
• (j) isoindolin-2-yl optionally substituted by halo;
• (k) —NRaRb, and
• (l) —O—CH2C(O)-3-11 membered heterocycloalkyl;
• wherein Ra and Rb are independently selected from:
• (a) H,
• (b) C1-C6 alkyl optionally substituted by OH, halo, CN, —C(O)OH, —C(O)O—(C1-C6alkyl), —C(O)O-(3-11 membered heterocycloalkyl), —C(O)O—(C1-C6 alkyl)-S—(C1-C6 alkyl), —S—(C1-C6 alkyl), naphthylenyl, —NRazRbz, —C(O)NRazRbz, oxo, —O—(C1-C6 alkyl), 5-6 membered heteroaryl optionally substituted by C1-C6 alkyl or halo, or benzo[1,3]dioxol-2-yl, or 3-11 membered heterocycloalkenyl optionally substituted by oxo;
• (c) —(C1-C6 alkylene)-3-6 membered cycloalkyl wherein the alkylene is optionally substituted by OH, halo, or CN;
• (d) —(C1-C6 alkylene)-phenyl wherein alkylene is optionally substituted by halo and the phenyl is optionally substituted by OH, halo, CF3, C1-C6 alkyl, —O—(C1-C6 alkyl), —S—(C1-C6 alkyl, or —O-phenyl;
• (e) —(C1-C6 alkylene)-4-6 membered heterocycloalkyl wherein the heterocycloalkyl is optionally substituted by halo, oxo, or C1-C6 alkyl;
• (f) —(C1-C6 alkylene)-O-phenyl wherein the phenyl is optionally substituted by halo, C1-C6 alkyl, or —O-phenyl;
• (g) —(C1-C6 alkyl)3-6 membered cycloalkyl optionally substituted by OH, halo, CN, or C1-C6 alkyl optionally substituted by OH or CN;
• (h) C2-C5 alkenyl;
• (i) 4-6 membered heterocycloalkyl optionally substituted by halo,
• (j) —(C1-C6 alkylene)-3-6 membered cycloalkyl substituted by hydroxymethyl,
• (k) phenyl,
• (l) —C(O)(C1-C6 alkyl),
• (m) —C(O)O(C1-C6 alkyl),
• (n) —C(O)O(3-6 membered cycloalkyl), and
• (o) —C(O)-phenyl,
• wherein Raz and Rbz are each independently selected from
• (a) H,
• (b) C1-C6 alkyl optionally substituted by OH, halo, CN, —C(O)OH, —C(O)O—(C1-C6alkyl), —C(O)O-(3-11 membered heterocycloalkyl), —C(O)O—(C1-C6 alkyl)-S—(C1-C6 alkyl), —S—(C1-C6 alkyl), naphthylenyl, -oxo, —O—(C1-C6 alkyl), 5-6 membered heteroaryl optionally substituted by C1-C6 alkyl or halo, or benzo[1,3]dioxol-2-yl, or 3-11 membered heterocycloalkenyl optionally substituted by oxo;
• (c) —(C1-C6 alkylene)-3-6 membered cycloalkyl wherein the alkylene is optionally substituted by OH, halo, or CN;
• (d) —(C1-C6 alkylene)-phenyl wherein alkylene is optionally substituted by halo and the phenyl is optionally substituted by OH, halo, CF3, C1-C6 alkyl, —O—(C1-C6 alkyl), —S—(C1-C6 alkyl, or —O-phenyl;
• (e) —(C1-C6 alkylene)-4-6 membered heterocycloalkyl wherein the heterocycloalkyl is optionally substituted by halo, oxo, or C1-C6 alkyl;
• (f) —(C1-C6 alkylene)-O-phenyl wherein the phenyl is optionally substituted by halo, C1-C6 alkyl, or —O-phenyl;
• (g) —(C1-C6 alkyl)3-6 membered cycloalkyl optionally substituted by OH, halo, CN, or C1-C6 alkyl optionally substituted by OH or CN;
• (h) C2-C5 alkenyl;
• (i) 4-6 membered heterocycloalkyl optionally substituted by halo,
• (j) —(C1-C6 alkylene)-3-6 membered cycloalkyl substituted by hydroxymethyl,
• (k) phenyl,
• (l) —C(O)(C1-C6 alkyl),
• (m) —C(O)O(C1-C6 alkyl),
• (n) —C(O)O(3-6 membered cycloalkyl), and
• (o) —C(O)-phenyl,
• with the following provisos:
• when R0, R00, and R01 are each H and Ring Q is
• where t1 is 0, then XA is not methyl, 2-methylpropan-2-ol, or tetrahydropyranyl.