Isopropanol → {2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-carbamic acid isopropyl ester

HRID 901570노트

반응식

HRID 901570 반응식
[N:1]([C:4]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH3:31])=[CH:22][N:21](S(C4C=CC(C)=CC=4)(=O)=O)[C:18]3=[N:19][CH:20]=2)=[CH:11][C:5]=1[C:6]([N:8]([CH3:10])[CH3:9])=[O:7])=[C:2]=[O:3].C(N(C(C)C)C(C)C)C.[CH:51]([OH:54])([CH3:53])[CH3:52]>C(Cl)Cl>[CH:51]([O:54][C:2](=[O:3])[NH:1][C:4]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]3[C:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH3:31])=[CH:22][NH:21][C:18]3=[N:19][CH:20]=2)=[CH:11][C:5]=1[C:6](=[O:7])[N:8]([CH3:9])[CH3:10])([CH3:53])[CH3:52]

참가 물질

5

반응물 3

HCID 3776IsopropanolHCID 81531DiisopropylethylamineHCID 597002582-isocyanato-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide

생성물 1

HCID 59700218{2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-carbamic acid isopropyl ester수율 48.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Into a 3 mL reation vial were added 2-isocyanato-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide (30 mg, 0.053 mmol), methylene chloride (1 mL), iPr2EtN (21 μL, 0.060 mmol), and isopropyl alcohol (50 μL, 6.5 mmol). The solution was stirred at room temperature for at least 12 h and monitored by HPLC. The reaction mixture was concentrated then re-dissolved in MeOH (1 mL), and cooled to 0° C. and treated with 100 μL 50% (w/w) aqueous KOH for 30 min or until Ts-removal was complete. The reaction was quenched by addition of 500 μL glacial acetic acid and then concentrated in vacuum. Purification by mass-triggered HPLC (formic acid ACN/H2O gradient) followed by lyophilization provided 12.2 mg of the title compound as a white powder. 1H-NMR (500 MHz, d6-DMSO) δ=11.91 (br.s, 1H), 8.96 (br.s., 1H), 8.53 (d, J=2.0 Hz, 1H), 8.15 (d, J=2.0 Hz, 1H), 7.73 (m, 3H), 7.60 (d, J=9.0 Hz, 1H), 7.59 (s, 1H), 7.29 (dd, J=1.5, 7.2 Hz, 1H), 7.12 (d, J=7 Hz, 1H), 7.04 (t, J=7 Hz, 1H), 4.84 (m, 1H), 3.81 (s, 3H), 2.97, 2,92 (br s, 6H), 1.23 (d, J=6, 6H); MS: m/z 473.1 [M+H+].

후처리

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthen re-dissolved in MeOH (1 mL)
  3. temperaturecooled to 0° C.
  4. additiontreated with 100 μL 50% (w/w) aqueous KOH for 30 min or until Ts-removal
  5. customThe reaction was quenched by addition of 500 μL glacial acetic acid
  6. concentrationconcentrated in vacuum
  7. customPurification by mass-triggered HPLC (formic acid ACN/H2O gradient)

출처 및 근거

ORD 기록
ord-ce92783bea734bc29ea1223a148c7aa3
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07361764B2

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