Diethyl Ether → Tris(1,1-dimethylethyl) 2-(2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate

HRID 1366541노트

반응식

HRID 1366541 반응식
[CH3:1][C:2]([N:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)([CH3:5])[CH2:3][NH2:4].C(N(C(C)C)CC)(C)C.[CH3:21][C:22]([O:25][C:26]([N:28]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[N:29]([C:37]1[C:42]([F:43])=[C:41](Cl)[N:40]=[C:39]([Cl:45])[N:38]=1)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:27])([CH3:24])[CH3:23].CCOCC>CN(C=O)C>[CH3:24][C:22]([O:25][C:26]([N:28]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[N:29]([C:37]1[C:42]([F:43])=[C:41]([NH:4][CH2:3][C:2]([CH3:1])([N:6]2[CH2:7][CH2:8][O:9][CH2:10][CH2:11]2)[CH3:5])[N:40]=[C:39]([Cl:45])[N:38]=1)[C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])=[O:27])([CH3:21])[CH3:23]

참가 물질

6

반응물 4

HCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 19896412-Methyl-2-(morpholin-4-yl)propan-1-amineHCID 58000755Tris(1,1-dimethylethyl) 2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate

생성물 1

HCID 86636980Tris(1,1-dimethylethyl) 2-(2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate수율 94%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of commercially-available [2-methyl-2-(4-morpholinyl)propyl]amine (0.158 g, 1.00 mmol) in DMF (10 mL) under a nitrogen atmosphere at 0° C., was added diisopropylethylamine (0.19 mL, 1.1 mmol) followed immediately by tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (0.497 g, 1.00 mmol). The reaction was allowed to reach room temperature and was stirred overnight. Then ether was added, and the mixture was washed with water. The aqueous layer was back extracted with ether, and the combined organics were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (5-60% ethyl acetate in hexanes, 1% triethylamine) to provide tris(1,1-dimethylethyl)2-(2-chloro-5-fluoro-6-{[2-methyl-2-(4-morpholinyl)propyl]amino}-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate as a clear oil (0.578 g, 94%). LCMS: (M+H)+=619.4.

후처리

  1. customto reach room temperature
  2. washthe mixture was washed with water
  3. extractionThe aqueous layer was back extracted with ether
  4. dry with materialthe combined organics were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by silica gel chromatography (5-60% ethyl acetate in hexanes, 1% triethylamine)

출처 및 근거

ORD 기록
ord-1b721ca6525e4c81b8e6d94e48535ad9
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07893056B2

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