Dichloromethane → N-(4-(3-amino-3-methylpiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride

HRID 408324ノート

反応式

HRID 408324 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:28]C(=O)OC(C)(C)C)[CH2:27][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:53]>CCCCO>[ClH:53].[NH2:28][C:22]1([CH3:21])[CH2:27][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 19691473Tert-butyl (3-methylpiperidin-3-yl)carbamateHCID 60205277N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide

生成物 1

HCID 60205511N-(4-(3-amino-3-methylpiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride収率 7.96%

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 (100 mg, 0.298 mmol), tert-butyl 3-methylpiperidin-3-ylcarbamate (192 mg, 0.895 mmol) and DIEA (0.052 mL, 0.298 mmol) in n-BuOH (3 mL) were stirred at 143° C. (bath) for 24 hours. The solvent was removed, and the residue was dissolved in ethyl acetate (20 mL), washed with water (10 mL), brine (10 mL), dried (sodium sulfate), and concentrated in vacuo. The residue obtained was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M+ column, 10-80% CH3CN/water gradient; 30 CV). The product isolated was dissolved in DCM (2 mL), and TFA (0.5 mL) was added. The mixture was stirred at room temperature for 1 hour. The solvent was then 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-methylpiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride (12.8 mg, 7.96% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 12.09 (s, 1H), 10.54 (s, 1H), 9.37 (s, 1H), 8.91 (d, 1H), 8.70 (m, 1H), 8.29 (s, 1H), 8.05 (s, 3H), 7.83 (m, 1H), 7.54 (s, 1H), 3.40 (m, 2H), 3.27 (m, 1H), 3.17 (m, 2H), 1.65 (m, 2H), 1.46 (m, 1H), 2.00 (s, 3H); LCMS (APCI+) m/z 429 (M+H)+.

後処理

  1. customThe solvent was removed
  2. dissolutionthe residue was dissolved in ethyl acetate (20 mL)
  3. washwashed with water (10 mL), brine (10 mL)
  4. dry with materialdried (sodium sulfate)
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. customwas purified by C-18 reverse phase flash chromatography (Biotage SP4 unit
  8. customThe product isolated
  9. customThe solvent was then removed
  10. dissolutionThe residue was dissolved in DCM (1 mL)
  11. addition2N HCl in ether (3 mL) was added
  12. customThe solid formed
  13. filtrationwas collected by filtration

出典と根拠

ORDレコード
ord-dbbaddbfe915483aa9275b28c2c9a6ce
出典データセット
uspto-grants-2014_06
特許番号
US08758830B2

反応ノート

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