Lithium hydroxide, monohydrate → {3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid

HRID 1261481노트

반응식

HRID 1261481 반응식
C([O:5][C:6](=[O:37])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:36])[C@@H:15]([N:22]2[CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][C:28]=3[C:31]([F:34])([F:33])[F:32])[C:23]2=[O:35])[CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:9]1)(C)(C)C.O.[OH-].[Li+]>O1CCCC1.O>[CH:17]1([CH2:16][C@H:15]([N:22]2[CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][C:28]=3[C:31]([F:33])([F:34])[F:32])[C:23]2=[O:35])[C:14]([NH:13][C:10]2[CH:11]=[CH:12][N:8]([CH2:7][C:6]([OH:37])=[O:5])[N:9]=2)=[O:36])[CH2:21][CH2:20][CH2:19][CH2:18]1

참가 물질

4

반응물 2

HCID 168937Lithium hydroxide, monohydrateHCID 70674336{3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid tert-butyl ester

생성물 1

HCID 70674337{3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid수율 98%

시약·촉매·용매 1

HCID 21881883Oxolane--water (1/1)용매

실험 절차

A mixture of {3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid tert-butyl ester (133 mg, 0.26 mmol, prepared as in Example 3) and lithium hydroxide monohydrate (22 mg, 0.52 mmol) in tetrahydrofuran:water (1:1, 10 mL) at room temperature was stirred for 2 h. The reaction mixture was then concentrated in vacuo and partitioned between a 1 N aqueous hydrochloric acid solution and ethyl acetate. The organic layer was then dried over magnesium sulfate, filtered to remove the drying agent, and the filtrate concentrated in vacuo to afford {3-[(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionylamino]-pyrazol-1-yl}-acetic acid (118 mg, 98%) as a white foam: HR-ES(+) m/e calcd for C22H23N4O4F3 [M+H]+ 465.1744, observed 465.1744; 1H NMR (400 MHz, DMSO-d6) δ ppm 10.93 (s, 1H), 8.01 (dd, J=7.67, 13.00 Hz, 2H), 7.69-7.80 (m, 1H), 7.59 (d, J=2.13 Hz, 1H), 6.45 (d, J=2.13 Hz, 1H), 4.95-5.12 (m, 2H), 4.81 (s, 2H), 4.72 (d, J=17.90 Hz, 1H), 1.09-2.11 (m, 11H).

후처리

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. custompartitioned between a 1 N aqueous hydrochloric acid solution and ethyl acetate
  3. dry with materialThe organic layer was then dried over magnesium sulfate
  4. filtrationfiltered
  5. customto remove the drying agent
  6. concentrationthe filtrate concentrated in vacuo

출처 및 근거

ORD 기록
ord-3650f97b73f746eba49f082883452b65
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08470866B2

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