Isobutyryl chloride → N-[4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-2-methylpropanamide

HRID 28900노트

반응식

HRID 28900 반응식
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:22]=[CH:21][C:20]([CH2:23][N:24]5[CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:19][CH:18]=4)=[CH:16][C:9]=23)[C:5]([C:29]2[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=2)=[N:4]1)[CH3:2].[CH3:36][CH:37]([CH3:41])[C:38](Cl)=[O:39]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:18]=[CH:19][C:20]([CH2:23][N:24]5[CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:21][CH:22]=4)=[CH:16][C:9]=23)[C:5]([C:29]2[CH:30]=[CH:31][C:32]([NH:33][C:38](=[O:39])[CH:37]([CH3:41])[CH3:36])=[CH:34][CH:35]=2)=[N:4]1)[CH3:2]

참가 물질

5

반응물 2

HCID 62325Isobutyryl chlorideHCID 68995250HCID 68995250, 화합물

생성물 1

HCID 58980014N-[4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-2-methylpropanamide수율 43%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

To a cloudy orange mixture of 4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)aniline (280 mg, 0.61 mmol) in dry CH2Cl2 (6 mL) was added TEA (253 uL, 1.82 mmol), DMAP (4 mg, 0.03 mmol) and 2-methylpropanoyl chloride (77 uL, 0.73 mmol). The reaction was stirred for 15 min at room temperature, quenched with water and diluted with CH2Cl2 and brine. The aqueous layer was extracted with CH2Cl2 followed by 1% MeOH in CH2Cl2 and the combined extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA). The clean fractions were neutralized with aqueous NaHCO3, extracted with three portions of CH2Cl2 followed by 1% MeOH in CH2Cl2, dried (Na2SO4), filtered and concentrated under reduced pressure to give 139 mg (43%) of the title product as a yellow solid. ESMS [M+H]+: 533.4.

후처리

  1. customquenched with water
  2. additiondiluted with CH2Cl2 and brine
  3. extractionThe aqueous layer was extracted with CH2Cl2
  4. dry with materialthe combined extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA)
  8. extractionextracted with three portions of CH2Cl2
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-8bd8488b582446d78503e7a4cf8c9447
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07419988B2

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