Dichloromethane → HCID 60205414、化合物

HRID 875746ノート

反応式

HRID 875746 の反応式
[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:21][C:22]1([NH:27]C(=O)OC(C)(C)C)[CH2:26][CH2:25][NH:24][CH2:23]1.CCN(C(C)C)C(C)C.C(O)(C(F)(F)F)=O.C(Cl)[Cl:52]>CCCCO>[ClH:52].[NH2:27][C:22]1([CH3:21])[CH2:26][CH2:25][N:24]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:19])[C:13]4[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=4)[C:4]=23)[CH2:23]1

参加物

7

反応物 5

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 10798104tert-butyl N-(3-methylpyrrolidin-3-yl)carbamateHCID 60205277N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide

生成物 1

HCID 60205414HCID 60205414、化合物収率 54%

試薬・触媒・溶媒 1

HCID 2631-Butanol溶媒

実験手順

N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.085 g, 0.254 mmol, Example 1, Step I), tert-butyl 3-methylpyrrolidin-3-ylcarbamate (0.152 g, 0.76 mmol) and DIEA (0.08 mL, 0.5 mmol) in n-BuOH (2 mL) were stirred at 156° C. (bath) for 6 hours. The solvent was removed, and the residue dissolved in ethyl acetate (20 mL), washed with water (10 mL), brine (10 mL) and dried over sodium sulfate. After removal of the solvent, the residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 10-80% CH3CN/water gradient; 25 CV) to give a solid. This solid was dissolved in DCM (3 mL), and TFA (0.5 mL) was added. The mixture was stirred at room temperature for 1 hour. The solvent was removed. The residue was dissolved in DCM (1 mL), and 2N HCl in ether (3 mL) was added. The solid formed was collected by filtration to give N-(4-(3-amino-3-methylpyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride (0.072 g, 54% yield) as a solid. 1H NMR (400 MHz, D2O) δ 9.16 (s, 1H), 8.84 (d, 1H), 8.78 (d, 1H), 8.22 (s, 1H), 7.98 (m, 1H), 7.40 (s, 1H), 3.80-3.94 (m, 3H), 3.62 (m, 1H), 2.04 (m, 1H), 1.85 (m, 1H), 1.23 (s, 3H); LCMS (APCI+) m/z 415 (M+H)+.

後処理

  1. customThe solvent was removed
  2. dissolutionthe residue dissolved in ethyl acetate (20 mL)
  3. washwashed with water (10 mL), brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. customAfter removal of the solvent
  6. customthe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit
  7. custom25 CV) to give a solid
  8. customThe solvent was removed
  9. dissolutionThe residue was dissolved in DCM (1 mL)
  10. addition2N HCl in ether (3 mL) was added
  11. customThe solid formed
  12. filtrationwas collected by filtration

出典と根拠

ORDレコード
ord-66db8fe46d3c49ff891160ed4822add8
出典データセット
uspto-grants-2015_03
特許番号
US08981085B2

反応ノート

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