Process for the preparation of a dpp-iv inhibitor

A crystalline form of (2S,3S,11bS)-1-(2-amino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-3-yl)-4(S)-fluoromethyl-pyrrolidin-2-one dihydrochloride characterized by a powder X-ray diffraction pattern obtained with a CuK radiation which comprises the following peaks:

• 6.0±0.2, 10.1±0.2, 12.1±0.2, 13.2±0.2, 14.5±0.2, 15.2±0.2, 15.5±0.2, 16.1±0.2, 16.4±0.2, 17.7±0.2, 19.5±0.2, 20.7±0.2, 21.6±0.2, 22.6±0.2, 27.3±0.2, 27.8±0.2 and 30.2±0.2 in 2θ (2Theta).

A crystalline form of (2S,3S,11bS)-1-(2-amino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-3-yl)-4(S)-fluoromethyl-pyrrolidin-2-one dihydrochloride characterized by an IR absorption spectrum having characteristic peaks expressed in cm−1 at approximately 3582 cm−1, 3440 cm−1, 3237 cm−1, 2726 cm−1, 2535 cm−1, 2477 cm−1, 1953 cm−1, 1681 cm−1, 1601 cm−1, 1575 cm−1, 1525 cm−1, 1491 cm−1, 1408 cm−1, 1308 cm−1 , 1260 cm−1, 1225 cm−1, 1193 cm−1, 1145 cm−1, 1130 cm−1, 1096 cm−1, 1054 cm−1, 1000 cm−1, 967 cm−1, 946 cm−1, 879 cm−1, 844 cm−1, 808 cm−1, 768cm−1 and 654 cm−1.

A crystalline DMF solvate form of (2S,3S,11bS)-1-(2-amino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-3-yl)-4(S)-fluoromethyl-pyrrolidin-2-one dihydrochloride characterized by a powder X-ray diffraction pattern obtained with a CuK radiation which comprises the following peaks:

• 6.8±0.2, 12.5±0.2, 13.5±0.2, 15.1±0.2, 17.4±0.2, 18.1±0.2, 18.4±0.2, 24.3±0.2, 24.8±0.2, 25.3±0.2, 27.2±0.2, 27.9±0.2, 28.1±0.2, 29.9±0.2 and 30.7±0.2 in 2θ (2Theta).

A crystalline DMF solvate form of (2S,3S,11bS)-1-(2-amino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-3-yl)-4(S)-fluoromethyl-pyrrolidin-2-one dihydrochloride characterized by an IR absorption spectrum having characteristic peaks expressed in cm−1 at approximately 3480 cm−1, 3376 cm−1, 2706 cm−1, 2682 cm−1, 2610 cm−1, 2574 cm−1, 2532 cm−1, 2381 cm−1, 1684 cm−1, 1659 cm−1, 1622 cm−1, 1574 cm−1, 1528 cm−1, 1487 cm−1, 1410 cm−1, 1383 cm−1, 1310 cm−1, 1267 cm−1, 1251 cm−1, 1229 cm−1, 1192 cm−1, 1135 cm−1, 1107 cm−1, 998 cm−1, 988 cm−1, 930 cm−1, 900 cm−1, 841 cm−1, 767 cm−1, 680 cm−1, and 667 cm−1.

Amorphous form of (2S,3S,11bS)-1-(2-amino-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-3-yl)-4(S)-fluoromethyl-pyrrolidin-2-one dihydrochloride characterized by an IR absorption spectrum having characteristic peaks expressed in cm−1 at approximately 3429 cm−1, 2507 cm−1, 1680 cm−1, 1612 cm−1, 1515 cm−1, 1310 cm−1, 1261 cm−1, 1246 cm−1, 1219 cm−1, 1127 cm−1, 994 cm−1, 964 cm−1, 945 cm−1, 888 cm−1, 860 cm−1, 842 cm−1, 767 cm−1, 685 cm−1 and 635 cm−1.