Trifluoroacetic acid → 2-Methyl-3'-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide

HRID 907534노트

반응식

HRID 907534 반응식
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)=[N:18][CH:17]=[CH:16][N:15]=2)[CH:10]([CH3:28])[CH2:9]1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C(N(CC)CC)C.[N:43]([C:46]1[CH:51]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:49]=[C:48]([C:56]([F:59])([F:58])[F:57])[CH:47]=1)=C=O>ClCCl>[F:53][C:52]([F:54])([F:55])[C:50]1[CH:51]=[C:46]([NH:43][C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[C:19]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=4)=[N:18][CH:17]=[CH:16][N:15]=3)[CH:10]([CH3:28])[CH2:9]2)=[O:7])[CH:47]=[C:48]([C:56]([F:57])([F:59])[F:58])[CH:49]=1

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 27333143,5-Bis(trifluoromethyl)phenyl isocyanateHCID 590139432-Methyl-3'-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid tert-butyl ester

생성물 1

HCID 103472422-Methyl-3'-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide수율 69%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

2-Methyl-3′-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (103 mgs, 0.27 mmol) was dissolved in dichloromethane (1.5 mL) to which was added TFA (2.0 mL) and the mixture stirred at room temperature for 1 hr until Boc removal was complete. The reaction mixture was concentrated in vacuo and redissolved in dichloromethane (1.0 mL) to which was added triethylamine (0.2 mL, 1.43 mmol) and 1-isocyanato-3,5-bis-trifluoromethyl-benzene (0.055 ml, 0.32 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the resulting residue purified by column chromatography (1:1 hexanes:EtOAc, followed by 1:3 hexanes:EtOAc) to give 98.9 mgs (69%) of 2-methyl-3′-(pyridin-4-ylmethoxy)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide as a white solid after lyophilization from H2O—AcCN. 1H NMR (CDCl3) 8.77 (d, 2H), 7.94 (s, 2H), 7.82 (d, 1H), 7.71 (d, 2H), 7.52 (d, 1H), 7.49 (s, 1H), 7.23 (s, 1H), 5.62 (s, 2H), 4.60 (m, 1H), 4.01 (m, 1H), 3.97-3.86 (m, 2H), 3.52-3.45 (m, 2H), 3.34 (m, 1H), 1.26 (d, 3H) ppm. LC-MS (MH+)=541.

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionredissolved in dichloromethane (1.0 mL) to which
  3. stirringThe mixture was stirred at room temperature overnight
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe resulting residue purified by column chromatography (1:1 hexanes:EtOAc, followed by 1:3 hexanes:EtOAc)

출처 및 근거

ORD 기록
ord-84f0f70147db4f8c8ef6df3eab6974a9
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08013156B2

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