4-Methylmorpholine → (S)-5-(3-(Difluoromethoxy)phenyl)-1-ethyl-N-(4-(morpholin-2-yl)phenyl)-1H-pyrazole-3-carboxamide hydrochloride

HRID 1520777노트

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HRID 1520777 반응식
[F:1][CH:2]([F:37])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[CH:14]=[C:13]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([C@@H:24]4[O:29][CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25]4)=[CH:20][CH:19]=3)=[O:16])[NH:12][N:11]=2)[CH:7]=[CH:8][CH:9]=1.[ClH:38].FC(F)O[C:42]1C=C(C2C=C(C(NC3C=CC([C@@H]4OCCNC4)=CC=3)=O)NN=2)C=C[CH:47]=1.Cl.N1CCO[C@@H](C2C=CC(NC(C3C=C(C4C=CC=CC=4)NN=3)=O)=CC=2)C1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CCCCCCC.O.CN(C=O)C>[ClH:38].[F:1][CH:2]([F:37])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[N:11]([CH2:42][CH3:47])[N:12]=[C:13]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([C@@H:24]4[O:29][CH2:28][CH2:27][NH:26][CH2:25]4)=[CH:20][CH:19]=3)=[O:16])[CH:14]=2)[CH:7]=[CH:8][CH:9]=1

참가 물질

9

반응물 5

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71087409(S)-3-(3-(Difluoromethoxy)phenyl)-N-(4-(morpholin-2-yl)phenyl)-1H-pyrazole-5-carboxamide hydrochlorideHCID 71087839(5)-Tert-butyl 2-(4-(3-(3-(difluoromethoxy)phenyl)-1H-pyrazole-5-carboxamido)phenyl)morpholine-4-carboxylateHCID 178479716HCID 178479716, 화합물

생성물 1

HCID 71087302(S)-5-(3-(Difluoromethoxy)phenyl)-1-ethyl-N-(4-(morpholin-2-yl)phenyl)-1H-pyrazole-3-carboxamide hydrochloride수율 58%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8900Heptane용매

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온도
60 °C

실험 절차

(S)-Tert-butyl 2-(4-(3-(3-(difluoromethoxy)phenyl)-1H-pyrazole-5-carboxamido)phenyl)morpholine-4-carboxylate: In a 25 mL round-bottomed flask, 3-(3-(difluoromethoxy)phenyl)-1H-pyrazole-5-carboxylic acid (515 mg, 2.03 mmol, Eq: 1.1) (preparation described in example 40), (5)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate (513 mg, 1.84 mmol, Eq: 1.00) (preparation described in example 1), N-Methylmorpholine (559 mg, 608 μl, 5.53 mmol, Eq: 3) and HBTU (1.05 g, 2.76 mmol, Eq: 1.5) were combined with DMF (2 ml) to give a yellow solution. The reaction mixture was stirred overnight at 60° C. The mixture was poured into water (10 ml) and extracted twice with EtOAc. The organic layers were washed with NaHCO3, brine, dried over MgSO4, filtered and concentrated in vacuo to give a brown crude mixture. This mixture was diluted with Heptane, stirred for 15 minutes and the suspension was filtered. The resulting solid was washed several times with Heptane to afford the desired compound as a brown solid (550 mg, 58.0%).

후처리

  1. customto give a yellow solution
  2. extractionextracted twice with EtOAc
  3. washThe organic layers were washed with NaHCO3, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a brown crude mixture
  8. stirringstirred for 15 minutes
  9. filtrationthe suspension was filtered
  10. washThe resulting solid was washed several times with Heptane

출처 및 근거

ORD 기록
ord-adcece56e475470181442a1c7dfdd7dc
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073911B2

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