N,N-Diethyl-2-propanamine → (S)-N-(1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-yl)-1-(4-fluorophenyl)-1H-pyrazole-3-carboxamide

HRID 1755263노트

반응식

HRID 1755263 반응식
Cl.[N:2]1[N:3]=[CH:4][N:5]2[CH:10]=[CH:9][N:8]=[C:7]([N:11]3[CH2:15][CH2:14][C@H:13]([NH2:16])[CH2:12]3)[C:6]=12.[F:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH:28]=[CH:27][C:26]([C:29](O)=[O:30])=[N:25]2)=[CH:20][CH:19]=1.C(N(CC)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[N:2]1[N:3]=[CH:4][N:5]2[CH:10]=[CH:9][N:8]=[C:7]([N:11]3[CH2:15][CH2:14][C@H:13]([NH:16][C:29]([C:26]4[CH:27]=[CH:28][N:24]([C:21]5[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=5)[N:25]=4)=[O:30])[CH2:12]3)[C:6]=12

참가 물질

7

반응물 4

HCID 521913N,N-Diethyl-2-propanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 289740501-(4-fluorophenyl)-1H-pyrazole-3-carboxylic acidHCID 86720539(S)-1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-amine hydrochloride salt

생성물 1

HCID 75202555(S)-N-(1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-yl)-1-(4-fluorophenyl)-1H-pyrazole-3-carboxamide수율 42.5%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a suspension of (S)-1-([1,2,4]triazolo[4,3-a]pyrazin-8-yl)pyrrolidin-3-amine hydrochloride salt (94 mg, 0.34 mmol), 1-(4-fluorophenyl)-1H-pyrazole-3-carboxylic acid (63 mg, 0.3 mmol) in DMF (5 mL) was added diethylisopropyl amine (650 mg, 5 mmol), followed by HATU (120 mg, 0.31 mmol). The resulting solution was stirred at room temperature for 1 h. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous solutions of KH2PO4 and NaHCO3, followed by brine. The organic layer was concentrated in vacuo and the residue purified by reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent) to give 50 mg of the title compound (42% yield) as a white solid.

후처리

  1. washwashed with saturated aqueous solutions of KH2PO4 and NaHCO3
  2. concentrationThe organic layer was concentrated in vacuo
  3. customthe residue purified by reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent)

출처 및 근거

ORD 기록
ord-032f07e8459649fa8d54800eb2230fd6
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169261B2

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