Trifluoroacetic acid → (2S)-2-(2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yloxy)butanamide

HRID 886500ノート

反応式

HRID 886500 の反応式
C([O:5][C:6](=O)[C@@H:7]([O:10][C:11]1[CH:34]=[CH:33][C:14]2[C:15]3[N:19]([CH2:20][CH2:21][O:22][C:13]=2[CH:12]=1)[CH:18]=[C:17]([C:23]1[N:24]([CH2:28][C:29]([F:32])([F:31])[F:30])[N:25]=[CH:26][N:27]=1)[N:16]=3)[CH2:8][CH3:9])(C)(C)C.C(O)(C(F)(F)F)=O.C[N:44](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+].C(N(CC)CC)C>C(Cl)Cl>[F:30][C:29]([F:32])([F:31])[CH2:28][N:24]1[C:23]([C:17]2[N:16]=[C:15]3[C:14]4[CH:33]=[CH:34][C:11]([O:10][C@@H:7]([CH2:8][CH3:9])[C:6]([NH2:44])=[O:5])=[CH:12][C:13]=4[O:22][CH2:21][CH2:20][N:19]3[CH:18]=2)=[N:27][CH:26]=[N:25]1

参加物

7

反応物 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58204893(S)-2-{2-[2-(2,2,2-Trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yloxy}-butyric acid tert-butyl ester

生成物 1

HCID 58205030(2S)-2-(2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yloxy)butanamide収率 39%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (S)-2-{2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yloxy}-butyric acid tert-butyl ester in DCM (3 mL) was added TFA (0.5 mL) and the reaction mixture stirred at RT for 16 h. The reaction mixture was concentrated in vacuo, and the residue dissolved in DMF (3 mL). HATU (217 mg, 0.56 mmol), ammonium chloride (46 mg, 0.85 mmol) and triethylamine (119 μL, 0.85 mmol) were added and the reaction mixture stirred at RT for 1 hour. The reaction mixture was concentrated in vacuo, the residue dissolved in ethyl acetate (10 mL) and the mixture washed with water extracting with ethyl acetate (3×10 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was subjected to flash chromatography (SiO2 gradient 0-10% methanol in EtOAc) then reverse phase preparative HPLC (C-18 column, 10-90% MeCN in water, 0.1% formic acid, 25 min gradient) to yield 494 as a white solid (49 mg, 39%). LCMS: RT=3.78 min, [M+H]+=437; 1H NMR (400 MHz, d6-DMSO) 8.22 (1H, d, J=8.9 Hz), 8.03 (1H, s), 7.96 (1H, s), 7.50 (1H, br s), 7.24 (1H, br s), 6.74 (1H, dd, J=8.9, 2.5 Hz), 6.51 (1H, d, J=2.5 Hz), 5.86 (2H, q, J=8.9 Hz), 4.52-4.39 (5H, m), 1.79 (2H, pent, J=7.2 Hz), 0.92 (3H, t, J=7.2 Hz)

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in DMF (3 mL)
  3. stirringthe reaction mixture stirred at RT for 1 hour
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. dissolutionthe residue dissolved in ethyl acetate (10 mL)
  6. washthe mixture washed with water extracting with ethyl acetate (3×10 mL)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customphase preparative HPLC (C-18 column, 10-90% MeCN in water, 0.1% formic acid, 25 min gradient)

出典と根拠

ORDレコード
ord-24fd6f5244304e298c6dd6435fc92b8a
出典データセット
uspto-grants-2012_08
特許番号
US08242104B2

反応ノート

読み込み中…