Method for producing oligonucleic acid compound

A method for producing a compound of general formula [C-1-1] comprising

• Step 1) a compound of general formula [B-1-1]:
• wherein
• each BP is the same or different and is an optionally protected nucleic acid base,
• p is an integer from 1 to 10,
• Q1 is a removable group under an acidic condition,
• each W is the same or different and is a lone pair of electrons, an oxygen atom or a sulfur atom,
• each X is the same or different and is a hydroxyl group protected with a removable group under a neutral condition, 1,1,3,3-tetra(C1-6 alkyl) guanidyl, C1-6 alkoxy, di(C1-6 alkyl)amino, mono(amino-C1-6 alkyl protected with a removable group under a basic condition)amino, di(amino-C1-6 alkyl protected with a removable group under a basic condition)amino, or a substituent having general formula [2]:
• wherein
• * is a binding position with a phosphorus atom,
• a is an integer from 0 to 2,
• E is CH2, CH-A1, or N-A2,
• A1 is C1-6 alkyl, mono(C1-6 alkyl)amino-C1-6 alkyl protected with a removable group under a basic condition, di(C1-6 alkyl)amino-C1-6 alkyl, tri (C1-6 alkyl) ammonio-C1-6 alkyl, amino protected with a removable group under a basic condition, mono(C1-6 alkyl)amino protected with a removable group under a basic condition, di(C1-6 alkyl)amino, tri (C1-6 alkyl) ammonio, amino substituted with amidino protected with a removable group under a basic condition, or a substituent having general formula [3]:
• wherein
• * is a binding position with E,
• b is an integer from 0 to 2,
• c is 0 or 1,
• R11 is C1-6 alkyl, and
• M is CH2, an oxygen atom, a sulfur atom, or N-(a removable group under a basic condition), and
• A2 is C1-6 alkyl, mono(C1-6 alkyl)amino-C1-6 alkyl protected with a removable group under a basic condition, di(C1-6 alkyl)amino-C1-6 alkyl, tri(C1-6 alkyl)ammonio-C1-6 alkyl, a removable group under a basic condition, aryl, or heteroaryl, is reacted with a compound of general formula [P]:
• wherein
• X is as defined above, and
• LG1 and LG2 are independently a leaving group
• to form a compound of general formula [B-1-2]:
• wherein p, BP, Q1, W, X and LG1 are as defined above, and
• Step 2) the compound of general formula [B-1-2] is reacted with a compound of general formula [A-1]:
• wherein
• BP, W and X are as defined above, and
• G is
• (1) a silyl substituent,
• (2) long-chain alkyl-carbonyl,
• (3) benzoyl substituted with 1 to 5 long-chain alkyloxy and/or long-chain alkenyloxy, or
• (4) a substituent having the following general formula [7]:
• wherein
• * is a binding position with T,
• Z is
• (1) (soluble polymer soluble in an organic solvent)-oxy,
• (2) (soluble polymer soluble in an organic solvent)-amino,
• (3) long-chain alkyloxy,
• (4) a solid phase carrier, or
• (5) a substituent having one of the following general formulae [8A] to [8N]:
• wherein
• * is a binding position with L,
• j is an integer from 0 to 4,
• k is an integer from 0 to 5,
• R8a is a hydrogen atom or C1-6 alkyl,
• R8b is the same or different and each is long-chain alkyl,
• R8c is the same or different and each is a substituent having one of the following general formulae [9A] to [9E]:
• wherein
• * is a binding position, and
• R9 is long-chain alkyl and/or long-chain alkenyl,
• R8d is the same or different and each is a hydrogen atom, a halogen, long-chain alkyl optionally substituted with 1 to 13 halogens, or long-chain alkyloxy optionally substituted with 1 to 13 halogens,
• R8e is
• (1) long-chain alkyl,
• (2) long-chain alkyl-carbonyl, or
• (3) benzoyl substituted with 1 to 5 long-chain alkyloxy and/or long-chain alkenyloxy, and
• R8f is
• (1) long-chain alkyl,
• (2) long-chain alkyl-carbonyl, or
• (3) long-chain alkenyl-carbonyl, and
• L is a substituent having general formula [10]:
• wherein
• * is a binding position with Z,
• ** is a binding position with T, and
• L1 is an unsubstituted or substituted C2-10 alkylene or an unsubstituted or substituted C6-10 arylene, and
• n is an integer from 1 to 50,
• T is a single bond or a substituent group having general formula [11]:
• wherein
• X and W are as defined above,
• * is a binding position with **O,
• ** is a binding position with G, and
• q is an integer from 0 to 10,
• provided that T is a single bond when G is a silyl substituent,
• to form a compound of general formula [C-1-1]:
• wherein n, p, BP, Q1, G, T, W, and X are as defined above.