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 907534ノート

反応式

HRID 907534 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-84f0f70147db4f8c8ef6df3eab6974a9
出典データセット
uspto-grants-2011_09
特許番号
US08013156B2

反応ノート

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