Phosgene → Cyclobutyl-6-bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate

HRID 2205924노트

반응식

HRID 2205924 반응식
[Br:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[NH:10][C:4]=2[CH:3]=1.[CH:17]1([O:21][C:22](Cl)=[O:23])[CH2:20][CH2:19][CH2:18]1.C1(O)CCC1.C(Cl)(Cl)=O>CN(C=O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[CH:17]1([O:21][C:22]([N:10]2[C:4]3[CH:3]=[C:2]([Br:1])[N:7]=[CH:6][C:5]=3[CH:8]=[C:9]2[C:11]2[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=2)=[O:23])[CH2:20][CH2:19][CH2:18]1

참가 물질

9

반응물 4

HCID 6371PhosgeneHCID 76218CyclobutanolHCID 5362587Cyclobutyl chloroformateHCID 867062766-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine

생성물 1

HCID 86706314Cyclobutyl-6-bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate수율 70.2%

시약·촉매·용매 4

HCID 962Water용매HCID 1140Toluene용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

6-bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine (Preparation 122, 100 mg, 0.36 mmol) was dissolved in dry DMF (1 ml). The solution was degassed and a solution of sodium bis(trimethylsilyl)amide (0.54 ml of a 1M solution in THF, 0.54 mmol) was added. After 20 minutes reaction, a solution of cyclobutylchloroformate [freshly prepared by stirring 40 mg of cyclobutanol with one equivalent of a 20% phosgene solution in toluene (0.275 ml) for 3 h, 0.55 mmol] was added. The reaction was stirred for 2 hours at room temperature then was diluted with ethyl acetate and water. The organic solution was washed with brine, dried over sodium sulphate and concentrated in vacuum. The crude product was purified on silica gel column chromatography eluting with 20% hexane in ethyl acetate to afford the title compound as a white powder (95 mg, 70.2%). 1H-NMR (500 MHz, CDCl3): δ 1.69 (m, 1H), 2.12 (m, 1H), 2.15 (m, 2H), 2.4 (m, 2H), 3.94 (s, 3H), 5.17 (quin, J=7.2 Hz, 1H), 6.54 (s, 1H), 7.6 (s, 1H), 7.62 (s, 1H), 8.14 (s. 1H), 8.51 (s, 1H)

후처리

  1. customThe solution was degassed
  2. additiona solution of sodium bis(trimethylsilyl)amide (0.54 ml of a 1M solution in THF, 0.54 mmol) was added
  3. customAfter 20 minutes reaction
  4. addition0.55 mmol] was added
  5. washThe organic solution was washed with brine
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated in vacuum
  8. customThe crude product was purified on silica gel column chromatography
  9. washeluting with 20% hexane in ethyl acetate

출처 및 근거

ORD 기록
ord-677ce9854cf44d1c92384232267d91b0
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09371319B2

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