Diisopropylethylamine → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-methyl-pyrrolo[3,2-b]pyridin-1-yl)-amide

HRID 2382087ノート

反応式

HRID 2382087 の反応式
[CH3:1][C:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]([NH2:11])[CH:3]=1.[F:12][C:13]1[CH:14]=[C:15]([C:19]2[N:24]=[C:23]([CH3:25])[C:22]([C:26](O)=[O:27])=[CH:21][N:20]=2)[CH:16]=[CH:17][CH:18]=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=O)C>[CH3:1][C:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]([NH:11][C:26]([C:22]2[C:23]([CH3:25])=[N:24][C:19]([C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([F:12])[CH:14]=3)=[N:20][CH:21]=2)=[O:27])[CH:3]=1

参加物

6

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 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acidHCID 685552333-Methyl-pyrrolo[3,2-b]pyridin-1-yl amine

生成物 1

HCID 592000172-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-methyl-pyrrolo[3,2-b]pyridin-1-yl)-amide収率 44%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 3-methyl-pyrrolo[3,2-b]pyridin-1-yl amine (75% pure) (240 mg, <1.63 mmol), 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (379 mg, 1.63 mmol), HATU (744 mg, 1.96 mmol) and DIPEA (388 mg, 4.89 mmol) in DMF (5 mL) is heated at 1500 C. for 1 h. The reaction is quenched with water, extracted with EtOAc. The organic layer is dried (Na2SO4), filtered and concentrated. The residue is chromatographed through silica gel eluting with 10% MeOH in DCM. The resulting product is recrystallized with ether to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-methyl-pyrrolo[3,2-b]pyridin-1-yl)-amide (197 mg, 44%). MS: 362 (M+H); 1H NMR (300 MHz, CD3OD): δ 9.14 (s, 1H), 8.40 (d, 1H), 8.36 (d, 1H), 8.22 (d, 1H), 7.85(d, 1H), 7.55 (q 1H), 7.47 (s, 1H), 7.25-7.34 (m, 2H), 2.83 (s, 3H), 2.42(s, 3H). IC50=2 nM.

後処理

  1. temperatureis heated at 1500 C
  2. customThe reaction is quenched with water
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer is dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is chromatographed through silica gel eluting with 10% MeOH in DCM
  8. customThe resulting product is recrystallized with ether

出典と根拠

ORDレコード
ord-447c8fceb5db41f88cc55655dd544fe9
出典データセット
uspto-grants-2012_09
特許番号
US08258130B2

反応ノート

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