1,2-Dichloroethane → [(2R)-3-(2-{2-chloro-5-fluoro-6-[(9aR)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide

HRID 1366565ノート

反応式

HRID 1366565 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:17][CH2:16][N:15]3[C@@H:10]([CH2:11][O:12][CH2:13][CH2:14]3)[CH2:9]2)[C:5]([F:18])=[C:4]([NH:19][NH2:20])[N:3]=1.[CH:21]1([CH2:26][C@H:27]([CH2:31][N:32]([CH:41]=[O:42])[O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:28](O)=[O:29])[CH2:25][CH2:24][CH2:23][CH2:22]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:19][NH:20][C:28](=[O:29])[C@H:27]([CH2:26][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25]2)[CH2:31][N:32]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:41]=[O:42])[C:5]([F:18])=[C:6]([N:8]2[CH2:17][CH2:16][N:15]3[C@@H:10]([CH2:11][O:12][CH2:13][CH2:14]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 86636988(9aR)-8-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)octahydropyrazino[2,1-c][1,4]oxazine

生成物 1

HCID 86636989[(2R)-3-(2-{2-chloro-5-fluoro-6-[(9aR)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide収率 91.5%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (9aR)-8-(2-chloro-5-fluoro-6-hydrazino-4-pyrimidinyl)octahydropyrazino[2,1-c][1,4]oxazine (1.41 g, 4.66 mmol) in DMF (45 mL) was added (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (1.36 g, 4.45 mmol), N-methylmorpholine (2.45 mL, 22.3 mmol), 1-hydroxy-7-azabenzotriazole (0.730 g, 5.364 mmol), and EDC (1.02 g, 5.32 mmol). The solution was stirred overnight and was then diluted with Et2O (200 mL). The mixture was washed with water (2×100 mL), and the combined aqueous phase was extracted with a fresh portion of Et2O (100 mL). This Et2O layer 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 dissolved in DCM (200 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was azeotroped with MeOH (50 mL) to give [(2R)-3-(2-{2-chloro-5-fluoro-6-[(9aR)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-pyrimidinyl}hydrazino)-2-(cyclopentylmethyl)-3-oxopropyl][(phenylmethyl)oxy]formamide (2.4027 g, 91% crude yield) as a red/orange oil. LCMS: (M+H)+: 590.2.

後処理

  1. washThe mixture was washed with water (2×100 mL)
  2. extractionthe combined aqueous phase was extracted with a fresh portion of Et2O (100 mL)
  3. washThis Et2O layer 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. dissolutionThe residue was dissolved in DCM (200 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was azeotroped with MeOH (50 mL)

出典と根拠

ORDレコード
ord-2ab7b39bbb7f4c1582b3d059cb1b2a2f
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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