Diisopropylethylamine → (2S)-2-{[6-{2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]hydrazino}-5-fluoro-2-(methyloxy)-4-pyrimidinyl]amino}-N,N-dimethylbutanamide

HRID 1366437Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][NH:11][C:12](=[O:32])[C@H:13]([CH2:26][CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:14][N:15]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:16]=[O:17])[C:3]=1[F:33].Cl.[NH2:35][C@@H:36]([CH2:42][CH3:43])[C:37]([N:39]([CH3:41])[CH3:40])=[O:38].C(N(C(C)C)CC)(C)C>CS(C)=O>[CH:27]1([CH2:26][C@H:13]([CH2:14][N:15]([CH:16]=[O:17])[O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:12]([NH:11][NH:10][C:4]2[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([NH:35][C@@H:36]([CH2:42][CH3:43])[C:37]([N:39]([CH3:41])[CH3:40])=[O:38])[C:3]=2[F:33])=[O:32])[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

Conditions

Temperature: 80 °C

Procedure

[(2R)-3-{2-[6-Chloro-5-fluoro-2-(methyloxy)-4-pyrimidinyl]hydrazino}-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (0.133 g, 0.28 mmol), (2S)-2-amino-N,N-dimethylbutanamide, hydrochloride salt (Example 83) (0.075 g, 0.45 mmol) and diisopropylethylamine (0.1 mL, 0.62 mmol) were stirred in DMSO (2 mL) overnight at 65° C. Then additional diisopropylethylamine (0.2 mL) was added, and the reaction was stirred for 7 days at 80° C. Purified by RP-HPLC to provide (2S)-2-{[6-{2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]hydrazino}-5-fluoro-2-(methyloxy)-4-pyrimidinyl]amino}-N,N-dimethylbutanamide (0.036 g, 23%). LCMS: (M+H)+=574.3.

Workup

customPurified by RP-HPLC

Sources & evidence

ORD record: ord-8ca2f7f07a3f4dc2ac39c3ab04ed1463
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07893056B2

Reaction notes

Loading…