Borane → HCID 59631388, compound

HRID 1431764Notes

Reaction equation

HRID 1431764 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:19][C:20]3[CH:21]=[C:22]([CH:28]=[C:29]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH:30]=3)[C:23]([N:25]([CH3:27])[CH3:26])=O)=[C:7]([CH3:18])[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)=[N:9]2)=[CH:4][CH:3]=1.B>C1COCC1>[CH3:27][N:25]([CH2:23][C:22]1[CH:21]=[C:20]([NH:19][C:6]2[C:5]3[C:10](=[CH:11][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[C:7]=2[CH3:18])[CH:30]=[C:29]([N:31]2[CH2:32][CH2:33][O:34][CH2:35][CH2:36]2)[CH:28]=1)[CH3:26]

Participants

4

Reactant 2

HCID 6331BoraneHCID 59631056HCID 59631056, compound

Product 1

HCID 59631388HCID 59631388, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirring solution of 3-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-ylamino)-N,N-dimethyl-5-morpholinobenzamide (0.074 g, 0.152 mmol) in THF (1.5 mL) was added 1M borane:THF complex (0.76 mL, 0.762 mmol). The reaction was stirred at 60° C. for 18 h, then cooled to 23° C., quenched with 0.7 mL concd HCl, and concd. To the resulting residue, 5 mL water was added as the reaction was stirred at 90° C. for one hour. The reaction was then basified with 1M sodium hydroxide, and the product was extracted twice with EtOAc. The combined organics were dried over magnesium sulfate and concd, affording a crude material that was purified by reverse-phase HPLC (0-70% acetonitrile in water). This yielded N-(3-((dimethylamino)methyl)-5-(4-morpholinyl)phenyl)-7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine as a yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.65-8.72 (1H, m), 8.47 (1H, s), 8.08 (1H, dd, J=9.2, 6.3 Hz), 7.96-8.01 (1H, m), 7.83-7.87 (1H, m), 7.69-7.73 (1H, m), 7.42-7.50 (2H, m), 6.38 (1H, s), 6.27-6.30 (1H, m), 6.09-6.11 (1H, m), 3.69 (4H, dd, J=5.6, 4.0 Hz), 3.23 (1H, br. s.), 2.99-3.05 (4H, m), 2.18 (3H, s), 2.10 (5H, br. s.). Mass Spectrum (ESI) m/e=472.2 (M+1).

Workup

  1. temperaturecooled to 23° C.
  2. customquenched with 0.7 mL concd HCl, and concd
  3. additionTo the resulting residue, 5 mL water was added as the reaction
  4. stirringwas stirred at 90° C. for one hour
  5. extractionthe product was extracted twice with EtOAc
  6. dry with materialThe combined organics were dried over magnesium sulfate and concd

Sources & evidence

ORD record
ord-c43bd63173d14aed9fe179cfa8e7ca69
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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