Diisopropylethylamine → 5-{1-[(2,5-difluorophenyl)acetyl]-4-fluoro-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 1910046노트

반응식

HRID 1910046 반응식
Cl.Cl.[F:3][C:4]1[C:12]([C:13]2[C:21]3[C:20]([NH2:22])=[N:19][CH:18]=[N:17][C:16]=3[N:15]([CH3:23])[CH:14]=2)=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7][NH:8]2.[F:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[CH2:32][C:33](O)=[O:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O>[F:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[CH2:32][C:33]([N:8]1[C:9]2[C:5](=[C:4]([F:3])[C:12]([C:13]3[C:21]4[C:20]([NH2:22])=[N:19][CH:18]=[N:17][C:16]=4[N:15]([CH3:23])[CH:14]=3)=[CH:11][CH:10]=2)[CH2:6][CH2:7]1)=[O:34]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 5228232,5-Difluorophenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668236155-(4-fluoro-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride

생성물 1

HCID 668238455-{1-[(2,5-difluorophenyl)acetyl]-4-fluoro-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine수율 36%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

A solution of 5-(4-fluoro-2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (100 mg, 0.281 mmol), 2,5-difluorophenylacetic acid (48.3 mg, 0.281 mmol), HATU (107 mg, 0.281 mmol), and DIEA (0.196 mL, 1.123 mmol) was stirred at room temperature overnight. The reaction mixture was poured into water (10 mL) and a precipitate formed. The precipitate was collected by filtration, and dried at the pump for 1 hour. The residue was adsorbed onto silica and purified by flash chromatography (0-10% MeOH in EtAc) to afford 5-{1-[(2,5-difluorophenyl)acetyl]-4-fluoro-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (44.2 mg, 36.0% yield) as a white solid. LC-MS (ES) m/z=438 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.23-3.29 (m, 2H), 3.75 (s, 3H), 3.97 (s, 2H), 4.36 (t, J=8.34 Hz, 2H), 5.78-6.19 (m, 2H), 7.13-7.32 (m, 5H), 7.89 (d, J=8.08 Hz, 1H), 8.15 (s, 1H).

후처리

  1. customa precipitate formed
  2. filtrationThe precipitate was collected by filtration
  3. customdried at the pump for 1 hour
  4. custompurified by flash chromatography (0-10% MeOH in EtAc)

출처 및 근거

ORD 기록
ord-2dec9c173ce849c2a61d5bb1a551bcee
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598156B2

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