(S)-1-Boc-3-methylpiperazine → n-Cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-4-{[(2s)-2-methylpiperazin-1-yl]methyl}-1-oxo-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide

HRID 906430Notes

Reaction equation

HRID 906430 reaction equation
[Si]([O:8][CH2:9][C:10]([CH3:40])([CH3:39])[CH2:11][N:12]1[CH:21]=[C:20]([CH2:22]O)[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:24]3[CH:25]=[C:26]([CH:33]=[C:34]([F:37])[C:35]=3[CH3:36])[C:27]([NH:29][CH:30]3[CH2:32][CH2:31]3)=[O:28])[CH:18]=2)[C:13]1=[O:38])(C(C)(C)C)(C)C.[CH3:41][C@@H:42]1[NH:47][CH2:46][CH2:45][N:44](C(OC(C)(C)C)=O)[CH2:43]1>>[CH:30]1([NH:29][C:27](=[O:28])[C:26]2[CH:25]=[C:24]([C:17]3[CH:18]=[C:19]4[C:14](=[CH:15][CH:16]=3)[C:13](=[O:38])[N:12]([CH2:11][C:10]([CH3:39])([CH3:40])[CH2:9][OH:8])[CH:21]=[C:20]4[CH2:22][N:47]3[CH2:46][CH2:45][NH:44][CH2:43][C@@H:42]3[CH3:41])[C:35]([CH3:36])=[C:34]([F:37])[CH:33]=2)[CH2:32][CH2:31]1

Participants

3

Reactant 2

HCID 7023035(S)-1-Boc-3-methylpiperazineHCID 673911003-[2-(3-{[tert-Butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-4-(hydroxymethyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]-N-cyclopropyl-5-fluoro-4-methylbenzamide

Product 1

HCID 59285262n-Cyclopropyl-3-fluoro-5-[2-(3-hydroxy-2,2-dimethylpropyl)-4-{[(2s)-2-methylpiperazin-1-yl]methyl}-1-oxo-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamideYield 14.1%

Procedure

The title compound was synthesised by a similar method to Example 26 h using 3-[2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-4-(hydroxymethyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]-N-cyclopropyl-5-fluoro-4-methylbenzamide (0.54 g), and tert-butyl (3S)-3-methylpiperazine-1-carboxylate (0.191 g). Purified by preparative HPLC (Waters Xbridge column using a 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as eluent) to give the title compound (0.072 g) as a solid.

Workup

  1. customwas synthesised by a similar method to Example 26 h
  2. customPurified by preparative HPLC (Waters Xbridge column

Sources & evidence

ORD record
ord-79c54de54ce649dc9f12f5cce847f39a
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

Loading…