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 1366549ノート

反応式

HRID 1366549 の反応式
[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

参加物

8

反応物 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

生成物 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]formamide収率 104.9%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-4824fedbaf6940f1b546ef77a5bc1330
出典データセット
uspto-grants-2011_02
特許番号
US07893056B2

反応ノート

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