Pyridine → N-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenyl)-3-(trifluoromethyl)piperazine-1-carboxamide

HRID 2067896ノート

反応式

HRID 2067896 の反応式
[F:1][CH:2]([F:25])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([NH2:24])[CH:18]=3)=[N:14][CH:15]=2)=[CH:6][CH:5]=1.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=[O:28].N1C=CC=CC=1.[CH2:45]([N:52]1[CH2:57][CH2:56][N:55](C(OCC)=O)[CH:54]([C:63]([F:66])([F:65])[F:64])[CH2:53]1)C1C=CC=CC=1.CSC.CS(O)(=O)=O>C(Cl)Cl>[F:25][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[N:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([NH:24][C:45]([N:52]4[CH2:57][CH2:56][NH:55][CH:54]([C:63]([F:66])([F:65])[F:64])[CH2:53]4)=[O:28])[CH:18]=3)=[N:12][CH:11]=2)=[CH:6][CH:5]=1

参加物

8

反応物 6

HCID 1049PyridineHCID 1068Dimethyl SulfideHCID 6395Methanesulfonic AcidHCID 821294-Nitrophenyl chloroformateHCID 58542194N1-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-yl)-4-methylbenzene-1,3-diamineHCID 68748441Ethyl 4-benzyl-2-(trifluoromethyl)piperazine-1-carboxylate

生成物 1

HCID 58542195N-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenyl)-3-(trifluoromethyl)piperazine-1-carboxamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

N1-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-yl)-4-methylbenzene-1,3-diamine 29a (0.4 mmol), 4-nitrophenyl chloroformate (0.48 mmol) and pyridine (0.8 mmol) in dry DCM (2 mL) are stirred at rt for 10 min. Then ethyl 2-(trifluoromethyl)piperazine-1-carboxylate 34b (0.48 mmol) is added and the reaction mixture is stirred for 2 h. After the reaction is complete, the mixture is diluted with 20 mL of DCM and washed with water. The organic layer is separated, dried over Na2SO4, filtered and concentrated under vacuum to afford a residue D11a. To this residue is added dimethylsulfide (1.2 mmol) and methanesulfonic acid (1.0 mL) and the resulting mixture is stirred at rt for 12 h. HPLC purification (ACN gradient 10-70%) affords D11 as a TFA salt. 1H NMR (400 MHz, d6-DMSO) δ 9.73 (s, 1H), 8.80 (s, 2H), 8.43 (s, 1H), 7.76 (d, J=8.4 Hz, 2H), 7.64 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.29 (d, J=8.4 Hz, 2H), 7.28 (t, J=74.0 Hz, 1H), 7.11 (d, J=8.4 Hz, 1H), 4.27 (m, 1H), 4.02 (m, 1H), 3.17 (m, 1H), 3.0 (s, 1H), 2.51 (m, 4H), 2.11 (s, 3H). MS (m/z) (M+1)+: 523.2.

後処理

  1. washwashed with water
  2. customThe organic layer is separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customto afford a residue D11a
  7. stirringthe resulting mixture is stirred at rt for 12 h
  8. customHPLC purification (ACN gradient 10-70%)

出典と根拠

ORDレコード
ord-b89d0da765044a119fb4a4c4ba6a8a13
出典データセット
uspto-grants-2012_10
特許番号
US08293757B2

反応ノート

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