Isobutyryl chloride → N-{3-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-isobutyramide

HRID 1506037노트

반응식

HRID 1506037 반응식
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH2:25])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:28](Cl)(=[O:32])[CH:29]([CH3:31])[CH3:30].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO.O>[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH:25][C:28](=[O:32])[CH:29]([CH3:31])[CH3:30])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

8

반응물 4

HCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 58266504HCID 58266504, 화합물

생성물 1

HCID 67203131N-{3-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-isobutyramide수율 12.4%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

A suspension of 3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-amine (80.9 mg, 0.226 mmol) in DCM (1.8 mL) was treated with isobutyryl chloride (26.3 μL, 0.249 mmol) and DIPEA (118 μL, 0.679 mmol). The reaction mixture was treated with saturated sodium bicarbonate and diluted with 20% MeOH in DCM and water. The layers were separated, the aqueous phase extracted into 20% MeOH in DCM, and the combined organic phase was dried over sodium sulfate and concentrated in vacuo. The resultant residue was dissolved in DCM/methanol, absorbed onto celite, and purified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid) to afford an off-white solid (12 mg, 12%). 1H NMR (DMSO-D6, 400 MHz): 12.03 (s, 1H), 10.32 (s, 1H), 8.95 (d, J=2.2 Hz, 1H), 8.90-8.85 (m, 2H), 8.62 (s, 1H), 7.79 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 3.48 (s, 2H), 2.79 (dt, J=6.7, 13.5 Hz, 1H), 2.36 (m, 4H), 1.58-1.46 (m, 4H), 1.41 (m, 2H), 1.14 (d, J=6.8 Hz, 6H). LCMS (Method D): RT=7.73 min, M+H+=428.

후처리

  1. customThe layers were separated
  2. extractionthe aqueous phase extracted into 20% MeOH in DCM
  3. dry with materialthe combined organic phase was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resultant residue was dissolved in DCM/methanol
  6. customabsorbed onto celite
  7. custompurified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid)

출처 및 근거

ORD 기록
ord-e3b155e6968743c0a579f523fceac7dc
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216980B2

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