Diisopropylethylamine → 1-[5-(4-Amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[6-(trifluoromethyl)pyridin-2-yl]ethanone

HRID 1910067ノート

反応式

HRID 1910067 の反応式
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[C:20]4[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=4[N:14]([CH3:22])[CH:13]=3)=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[F:23][C:24]([F:36])([F:35])[C:25]1[N:30]=[C:29]([CH2:31][C:32](O)=[O:33])[CH:28]=[CH:27][CH:26]=1.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>CN(C)C=O.O>[CH3:22][N:14]1[C:15]2[N:16]=[CH:17][N:18]=[C:19]([NH2:21])[C:20]=2[C:12]([C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[N:3]([C:32](=[O:33])[CH2:31][C:29]2[CH:28]=[CH:27][CH:26]=[C:25]([C:24]([F:23])([F:36])[F:35])[N:30]=2)[CH2:4][CH2:5]3)=[CH:13]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 534015132-(6-(Trifluoromethyl)pyridin-2-yl)acetic acidHCID 668234705-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine dihydrochloride

生成物 1

HCID 668234781-[5-(4-Amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[6-(trifluoromethyl)pyridin-2-yl]ethanone収率 39.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (150 mg, 0.443 mmol), [6-(trifluoromethyl)-2-pyridinyl]acetic acid (91 mg, 0.443 mmol), HATU (169 mg, 0.443 mmol), and DIEA (0.310 mL, 1.774 mmol) in N,N-Dimethylformamide (DMF) (3 mL) were stirred overnight at room temperature. LCMS analysis at this time indicated good conversion, so the reaction mixture was poured into water (10 mL) and stirred for 30 min. The resulting precipitate was collected by filtration, dried at the pump for an hour, adsorbed onto silica and purified by flash chromatography (0-10% MeOH in EtOAc) to afford 7-methyl-5-(1-{[6-(trifluoromethyl)-2-pyridinyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (80 mg, 39.9% yield) as a beige solid. LC-MS (ES) m/z=453 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.26 (t, J=8.34 Hz, 2H), 3.74 (s, 3H), 4.21 (s, 2H), 4.31 (t, J=8.46 Hz, 2H), 5.85-6.26 (m, 2H), 7.23 (d, J=8.34 Hz, 1H), 7.26 (s, 1H), 7.34 (s, 1H), 7.71 (d, J=7.83 Hz, 1H), 7.83 (d, J=7.58 Hz, 1H), 8.05-8.13 (m, 2H), 8.15 (s, 1H).

後処理

  1. filtrationThe resulting precipitate was collected by filtration
  2. customdried at the pump for an hour
  3. custompurified by flash chromatography (0-10% MeOH in EtOAc)

出典と根拠

ORDレコード
ord-261a87dc0bdf44099f55366c40ca5404
出典データセット
uspto-grants-2013_12
特許番号
US08598156B2

反応ノート

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