1,2-Dichloroethane → [(2R)-3-(2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide

HRID 1366549노트

반응식

HRID 1366549 반응식
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH:12]3[C:10]([N:14]([CH3:16])[CH3:15])([CH2:11]3)[CH2:9]2)[C:5]([F:17])=[C:4]([NH:18][NH2:19])[N:3]=1.[CH:20]1([CH2:25][C@H:26]([CH2:30][N:31]([CH:40]=[O:41])[O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:27](O)=[O:28])[CH2:24][CH2:23][CH2:22][CH2:21]1.CN1CCOCC1.ON1C2N=CC=CC=2N=N1.C(Cl)CCl>CN(C=O)C.CCOCC>[Cl:1][C:2]1[N:3]=[C:4]([NH:18][NH:19][C:27](=[O:28])[C@H:26]([CH2:25][CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24]2)[CH2:30][N:31]([O:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:40]=[O:41])[C:5]([F:17])=[C:6]([N:8]2[CH2:13][CH:12]3[C:10]([N:14]([CH3:16])[CH3:15])([CH2:11]3)[CH2:9]2)[N:7]=1

참가 물질

8

반응물 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acidHCID 87210194racemic 3-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-N,N-dimethyl-3-azabicyclo[3.1.0]hexan-1-amine

생성물 1

HCID 86636983[(2R)-3-(2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide수율 104.9%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

실험 절차

To a solution of racemic 3-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)-N,N-dimethyl-3-azabicyclo[3.1.0]hexan-1-amine (0.3374 g, 1.177 mmol) in DMF (10 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (0.3257 g, 1.067 mmol), N-methylmorpholine (0.590 mL, 5.366 mmol), 1-hydroxy-7-azabenzotriazole (0.174 g, 1.278 mmol), and EDC (0.245 g, 1.278 mmol). The mixture was stirred overnight, and then diluted with Et2O (100 mL). The mixture was washed with water (2×50 mL), and the combined aqueous phase was extracted with a fresh portion of Et2O (50 mL). This organic phase was washed with a fresh portion of water (50 mL), and the combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was diluted with DCM (200 mL), and dried over anhydrous Na2SO4. The mixture was filtered and concentrated in vacuo to provide crude [(2R)-3-(2-{2-chloro-6-[1-(dimethylamino)-3-azabicyclo[3.1.0]hex-3-yl]-5-fluoro-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (0.6428 g, >100% crude yield, mixture of diastereomers) as an orange oil. LCMS: (M+H)+: 574.2.

후처리

  1. washThe mixture was washed with water (2×50 mL)
  2. extractionthe combined aqueous phase was extracted with a fresh portion of Et2O (50 mL)
  3. washThis organic phase was washed with a fresh portion of water (50 mL)
  4. dry with materialthe combined organic phase was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionThe residue was diluted with DCM (200 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationThe mixture was filtered
  10. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-4824fedbaf6940f1b546ef77a5bc1330
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07893056B2

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