Formaldehyde → (R)-N-Cyclopropyl-3-(2-(cyclopropylmethyl)-4-((3-(hydroxymethyl)-4-methylpiperazin-1-yl)methyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-5-fluoro-4-methylbenzamide

HRID 907316Notes

Reaction equation

HRID 907316 reaction equation
[CH:1]1([NH:4][C:5](=[O:38])[C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[C:20](=[O:24])[N:19]([CH2:25][CH:26]3[CH2:28][CH2:27]3)[CH:18]=[C:17]4[CH2:29][N:30]3[CH2:35][CH2:34][NH:33][C@@H:32]([CH2:36][OH:37])[CH2:31]3)[CH:7]=2)[CH2:3][CH2:2]1.C=O.[C:41](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>ClCCl>[CH:1]1([NH:4][C:5](=[O:38])[C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[C:20](=[O:24])[N:19]([CH2:25][CH:26]3[CH2:28][CH2:27]3)[CH:18]=[C:17]4[CH2:29][N:30]3[CH2:35][CH2:34][N:33]([CH3:41])[C@@H:32]([CH2:36][OH:37])[CH2:31]3)[CH:7]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 24994903(R)-N-Cyclopropyl-3-(2-(cyclopropylmethyl)-4-((3-(hydroxymethyl)piperazin-1-yl)methyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-5-fluoro-4-methylbenzamide

Product 1

HCID 57551779(R)-N-Cyclopropyl-3-(2-(cyclopropylmethyl)-4-((3-(hydroxymethyl)-4-methylpiperazin-1-yl)methyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-5-fluoro-4-methylbenzamideYield 85.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product of Example 85 (80 mg) was dissolved in dichloromethane (10 mL). Formaldehyde (0.057 mL) and sodium triacetoxyborohydride (98 mg) were then added and the mixture stirred for 4 hours. Water (10 mL) was then added and the mixture extracted with dichloromethane (30 mL). The organics were combined and evaporated under reduced pressure. The residue was purified by HPLC to give the title compound as a solid (70 mg).

Workup

  1. extractionthe mixture extracted with dichloromethane (30 mL)
  2. customevaporated under reduced pressure
  3. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-eba2a6c0beec4372a732b981ed47cdb6
Source dataset
uspto-grants-2011_09
Patent number
US08012979B2

Reaction notes

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