Triethylamine → (S)-{2-(4-Chlorobenzyl)-3-oxo-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propyl}-carbamic acid tert-butyl ester

HRID 1192348노트

반응식

HRID 1192348 반응식
CCN(CC)CC.Cl.Cl.[N:10]1([C:16]2[C:17]3[CH:24]=[CH:23][NH:22][C:18]=3[N:19]=[CH:20][N:21]=2)[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.[C:25]([O:29][C:30]([NH:32][CH2:33][C@H:34]([CH2:38][C:39]1[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=1)[C:35](O)=[O:36])=[O:31])([CH3:28])([CH3:27])[CH3:26].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O>[C:25]([O:29][C:30](=[O:31])[NH:32][CH2:33][C@H:34]([CH2:38][C:39]1[CH:40]=[CH:41][C:42]([Cl:45])=[CH:43][CH:44]=1)[C:35](=[O:36])[N:13]1[CH2:12][CH2:11][N:10]([C:16]2[C:17]3[CH:24]=[CH:23][NH:22][C:18]=3[N:19]=[CH:20][N:21]=2)[CH2:15][CH2:14]1)([CH3:28])([CH3:26])[CH3:27]

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 40153909(S)-3-((Tert-butoxycarbonyl)amino)-2-(4-chlorobenzyl)propanoic acidHCID 675378564-(Piperazin-1-yl)-1H-pyrrolo[2,3-d]pyrimidine dihydrochloride

생성물 1

HCID 67540648(S)-{2-(4-Chlorobenzyl)-3-oxo-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propyl}-carbamic acid tert-butyl ester

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

NEt3 (150 μL, 1.1 mmol) was added to a stirred suspension of 4-Piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidine dihydrochloride (100 mg, 0.36 mmol), (S)-2-(tert-Butoxycarbonylamino-methyl)-3-(4-chlorophenyl)-propionic acid (130 mg, 0.40 mmol), EDCI (83 mg, 0.44 mmol) and HOBt (59 mg, 0.44 mmol) in DMF (15 mL) at RT. Stirred at RT overnight. Poured into EtOAc (100 mL), washed with water (100 mL), 1N NaOH (50 mL), dried over Na2SO4, concentrated in vacuo, purified by column chromatography on silica (100% EtOAc) to give (S)-{2-(4-Chlorobenzyl)-3-oxo-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propyl}-carbamic acid tert-butyl ester. LCMS (APCI+) m/z 499 [M+H]+; Rt: 2.70 minutes. This was taken up into DCM (50 mL) and stirred with TFA (5 mL) overnight. Poured into EtOAc (100 mL) and washed with 1N NaOH (2×100 mL), dried over Na2SO4 and concentrated in vacuo. Formed HCl salt (Et2O.HCl, 2M in diethyl ether) to give (S)-2-Aminomethyl-3-(4-chlorophenyl)-1-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazin-1-yl]-propan-1-one dihydrochloride (100 mg, 59%.) LCMS (APCI+) m/z 399 [M+H]+; Rt: 1.82 min. [Free base: 1H NMR (CDCl3, 400 MHz) δ 9.97 (1H, br.s), 8.32 (1H, s), 7.24 (2H, d, J 7.4 Hz), 7.13 (2H, d, J 7.4 Hz), 7.09 (1H, d, J 2.4 Hz), 6.45 (1H, d, J 2.3 Hz), 4.00-3.68 (5H, m), 3.60-3.53 (1H, m), 3.46-3.40 (1H, m), 3.33-3.27 (1H, m), 3.16-3.05 (2H, m), 2.92-2.83 (2H, m), 2.77 (1H, dd, J 13.3 and 5.5 Hz.)]

후처리

  1. washwashed with water (100 mL), 1N NaOH (50 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. custompurified by column chromatography on silica (100% EtOAc)

출처 및 근거

ORD 기록
ord-b6796e9513c04f3cbd38d3efdc0caf42
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680114B2

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