Diisopropylethylamine → Tert-butyl(2s)-2-(4-chlorophenyl)-3-(4-(3-(2,3-dihydroxypropoxy)-1h-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

HRID 387577노트

반응식

HRID 387577 반응식
CCN(C(C)C)C(C)C.Cl.Cl.[N:12]1([C:18]2[CH:23]=[CH:22][N:21]=[C:20]3[NH:24][N:25]=[C:26]([O:27][CH2:28][CH:29]([OH:32])[CH2:30][OH:31])[C:19]=23)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.[C:33]([O:37][C:38]([N:40]([CH:53]([CH3:55])[CH3:54])[CH2:41][C@H:42]([C:46]1[CH:51]=[CH:50][C:49]([Cl:52])=[CH:48][CH:47]=1)[C:43](O)=[O:44])=[O:39])([CH3:36])([CH3:35])[CH3:34].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[Cl:52][C:49]1[CH:50]=[CH:51][C:46]([C@H:42]([C:43]([N:15]2[CH2:16][CH2:17][N:12]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]4[NH:24][N:25]=[C:26]([O:27][CH2:28][CH:29]([OH:32])[CH2:30][OH:31])[C:19]=34)[CH2:13][CH2:14]2)=[O:44])[CH2:41][N:40]([CH:53]([CH3:54])[CH3:55])[C:38](=[O:39])[O:37][C:33]([CH3:35])([CH3:34])[CH3:36])=[CH:47][CH:48]=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 687574603-(4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-yloxy)propane-1,2-diol dihydrochloride

생성물 1

HCID 68766483Tert-butyl(2s)-2-(4-chlorophenyl)-3-(4-(3-(2,3-dihydroxypropoxy)-1h-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

DIEA (0.0514 mL, 0.295 mmol) was added to 3-(4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-3-yloxy)propane-1,2-diol dihydrochloride (0.030 g, 0.0737 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.0252 g, 0.0737 mmol, see Example B) and TBTU (0.0284 g, 0.0885 mmol) in DCM (1 mL) and stirred at room temperature for 2 hours. The reaction was concentrated to dryness. The resulting residue was dissolved in THF:MeOH (2 mL, 1:1), and a LiOH solution (1 mL, 2M) was added. The solution was stirred for 30 minutes, followed by the addition of ether (20 mL). The organic layer was separated, washed with brine (10 mL), and dried over sodium sulfate. After removal of the solvent, the resulting residue was purified by column chromatography (ethyl acetate:MeOH, 20:1) to give tert-butyl(2S)-2-(4-chlorophenyl)-3-(4-(3-(2,3-dihydroxypropoxy)-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 (0.4 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 2N HCl in ether (1 mL) was added. The resulting solid was collected by filtration to give (2S)-2-(4-chlorophenyl)-1-(4-(3-(2,3-dihydroxypropoxy)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one dihydrochloride (0.014 g, 33%). MS APCI (+) m/z 517.2 detected.

후처리

  1. concentrationThe reaction was concentrated to dryness
  2. dissolutionThe resulting residue was dissolved in THF
  3. additionMeOH (2 mL, 1:1), and a LiOH solution (1 mL, 2M) was added
  4. stirringThe solution was stirred for 30 minutes
  5. additionfollowed by the addition of ether (20 mL)
  6. customThe organic layer was separated
  7. washwashed with brine (10 mL)
  8. dry with materialdried over sodium sulfate
  9. customAfter removal of the solvent
  10. customthe resulting residue was purified by column chromatography (ethyl acetate:MeOH, 20:1)

출처 및 근거

ORD 기록
ord-35a9b72173694c05a7b501fdd8299dc8
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372842B2

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