Diisopropylethylamine → (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

HRID 1630082

반응식

HRID 1630082 반응식
[C:1]([C@H:3]1[CH2:7][NH:6][C@H:5]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)=[O:9])[CH2:4]1)#[N:2].[N:25]1([CH2:30][C:31](O)=[O:32])[CH:29]=[N:28][CH:27]=[N:26]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N:25]1([CH2:30][C:31]([N:6]2[CH2:7][C@H:3]([C:1]#[N:2])[CH2:4][C@H:5]2[C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)=[CH:15][CH:16]=2)=[O:9])=[O:32])[CH:29]=[N:28][CH:27]=[N:26]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 18101801,2,4-Triazole-1-acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67010040(2S,4R)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

생성물 1

HCID 67010058(2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide수율 62%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A flask was charged with (2S,4R)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (0.88 g, 2.69 mmol), prepared as in Reference 8, 2-(1H-1,2,4-triazol-1-yl)acetic acid (340 mg, 2.69 mmol), DIEA (3.0 mL, 17 mmol), HATU (1.12 g, 2.96 mmol) and DMF (10 mL). The reaction mixture was stirred at ambient temperature for 20 minutes and then quenched with saturated sodium bicarbonate (aq., 10 mL). The mixture was ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL) and then brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3) to give (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (0.72 g, 1.66 mmol, 62% yield) as an off-white solid. 1H-NMR (400 MHz, DMSO-d6): 10.20 (s, 1H), 8.46 (s, 1H), 7.97 (s, 1H), 7.57 (d, J=8.8 Hz, 2H), 7.22-7.17 (m, 2H), 7.03-6.95 (m, 4H), 5.38-5.26 (m, 2H), 4.59-4.55 (m, 1H), 4.08-3.94 (m, 2H), 3.84-3.50 (m, 2H), 2.39-2.32 (m, 1H). MS (EI) for C22H19FN6O3. found 517.3 (MH+).

후처리

  1. customquenched with saturated sodium bicarbonate (aq., 10 mL)
  2. washthe extract was washed with deionized water (10 mL)
  3. dry with materialbrine (10 mL), dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customProduct was purified from the residue by chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3)

출처 및 근거

ORD 기록
ord-b0fac0cb0e92469aa3634e706aa48003
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791102B2

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