Diisopropylethylamine → tris(1,1-dimethylethyl) 2-{2-chloro-5-fluoro-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate

HRID 1366682ノート

反応式

HRID 1366682 の反応式
Cl.[CH3:2][C@H:3]1[CH2:8][O:7][CH2:6][CH2:5][NH:4]1.[CH3:9][C:10]([O:13][C:14]([N:16]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[N:17]([C:25]1[C:30]([F:31])=[C:29](Cl)[N:28]=[C:27]([Cl:33])[N:26]=1)[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:15])([CH3:12])[CH3:11].C(N(CC)C(C)C)(C)C>CN(C=O)C.CCOCC>[CH3:12][C:10]([O:13][C:14]([N:16]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[N:17]([C:25]1[C:30]([F:31])=[C:29]([N:4]2[CH2:5][CH2:6][O:7][CH2:8][C@@H:3]2[CH3:2])[N:28]=[C:27]([Cl:33])[N:26]=1)[C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])=[O:15])([CH3:9])[CH3:11]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 53486469(3S)-3-methylmorpholine hydrochlorideHCID 58000755Tris(1,1-dimethylethyl) 2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate

生成物 1

HCID 86637029tris(1,1-dimethylethyl) 2-{2-chloro-5-fluoro-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate収率 79%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (3S)-3-methylmorpholine hydrochloride (0.2059 g, 1.496 mmol) in DMF (7.5 mL) was added tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (0.7451 g, 1.498 mmol), and N,N-diisopropylethylamine (0.575 mL, 3.301 mmol). The solution was stirred overnight, and then diluted with Et2O (150 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 Et2O layer was washed with a fresh portion of water (50 mL), and the combined organic phase was diluted with DCM (50 mL), dried over anhydrous Na2SO4, filtered, concentrated in vacuo, and azeotroped with EtOAc. The solid was collected by vacuum filtration and washed with hexanes. The supernatant was concentrated in vacuo, and purified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes; 1% Et3N). The desired fractions were concentrated in vacuo, and the resulting solid was collected by vacuum filtration, washed with hexanes, and combined with the first crop of solid to give tris(1,1-dimethylethyl)2-{2-chloro-5-fluoro-6-[(3S)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate (0.6610 g, 79%) as a white solid. LCMS: (M+H)+: 562.2.

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 Et2O layer was washed with a fresh portion of water (50 mL)
  4. additionthe combined organic phase was diluted with DCM (50 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customazeotroped with EtOAc
  9. filtrationThe solid was collected by vacuum filtration
  10. washwashed with hexanes
  11. concentrationThe supernatant was concentrated in vacuo
  12. custompurified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes; 1% Et3N)
  13. concentrationThe desired fractions were concentrated in vacuo
  14. filtrationthe resulting solid was collected by vacuum filtration
  15. washwashed with hexanes

出典と根拠

ORDレコード
ord-da3ce1630d764954bb0bd07755695c60
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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