Diisopropylethylamine → (S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

HRID 387562노트

반응식

HRID 387562 반응식
CCN(C(C)C)C(C)C.Cl.Cl.[F:12][C:13]1[CH:14]=[C:15]([C:19]2[C:20]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[C:21]3[CH:27]=[N:26][NH:25][C:22]3=[N:23][CH:24]=2)[CH:16]=[CH:17][CH:18]=1.[C:34]([O:38][C:39]([N:41]([CH:54]([CH3:56])[CH3:55])[CH2:42][C@H:43]([C:47]1[CH:52]=[CH:51][C:50]([Cl:53])=[CH:49][CH:48]=1)[C:44](O)=[O:45])=[O:40])([CH3:37])([CH3:36])[CH3:35].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[Cl:53][C:50]1[CH:51]=[CH:52][C:47]([C@H:43]([C:44]([N:31]2[CH2:32][CH2:33][N:28]([C:20]3[C:19]([C:15]4[CH:16]=[CH:17][CH:18]=[C:13]([F:12])[CH:14]=4)=[CH:24][N:23]=[C:22]4[NH:25][N:26]=[CH:27][C:21]=34)[CH2:29][CH2:30]2)=[O:45])[CH2:42][N:41]([CH:54]([CH3:55])[CH3:56])[C:39](=[O:40])[O:38][C:34]([CH3:36])([CH3:35])[CH3:37])=[CH:48][CH:49]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acidHCID 687569845-(3-fluorophenyl)-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride

생성물 1

HCID 68765028(S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

DIEA (d 0.742; 0.0790 mL, 0.454 mmol) was added to a solution of 5-(3-fluorophenyl)-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (0.070 g, 0.113 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.0388 g, 0.113 mmol, see Example B) and TBTU (0.0437 g, 0.136 mmol) in DCM (1 mL) and stirred at room temperature for 18 hours. The mixture was directly loaded onto a silica column and purified by chromatography (hexane:ethyl acetate, 1:1) to give (S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate as a solid. The solid was dissolved in DCM (1 mL), and TFA (0.2 mL) was added. The mixture was stirred at room temperature for 1 hour and then concentrated to dryness. The resulting residue was dissolved in DCM (0.5 mL), and HCl in ether (1 mL, 2N) was added. The resulting solid was collected by filtration to give (S)-2-(4-chlorophenyl)-1-(4-(5-(3-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one dihydrochloride (0.022 g, 32%). MS APCI (+) m/z 521.4 detected.

후처리

  1. custompurified by chromatography (hexane:ethyl acetate, 1:1)

출처 및 근거

ORD 기록
ord-5cb4e6fe1e834386bdaa9356c0546024
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372842B2

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