Sodium hydride → Gsk-189254

HRID 222687Notes

Reaction equation

HRID 222687 reaction equation
[H-].[Na+].[CH:3]1([N:7]2[CH2:13][CH2:12][C:11]3[CH:14]=[C:15]([OH:18])[CH:16]=[CH:17][C:10]=3[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.Cl[C:20]1[CH:29]=[CH:28][C:23]([C:24]([NH:26][CH3:27])=[O:25])=[CH:22][N:21]=1>CS(C)=O>[CH:3]1([N:7]2[CH2:13][CH2:12][C:11]3[CH:14]=[C:15]([O:18][C:20]4[CH:29]=[CH:28][C:23]([C:24]([NH:26][CH3:27])=[O:25])=[CH:22][N:21]=4)[CH:16]=[CH:17][C:10]=3[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 100820813-Cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[D]azepin-7-OLHCID 123642306-Chloro-N-methylnicotinamide

Product 1

HCID 9798547Gsk-189254

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

Sodium hydride (60% disp. in mineral oil, 60 mg, 1.5 mmol) was added to a stirred solution of 3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol (E3) (200 mg, 0.9 mmol) in dimethyl sulfoxide (10 ml). After 0.5 hours, 6-chloro-N-methyl-nicotinamide (D10) (400 mg, 2.5 mmol) was added and the reaction mixture was heated to 120° C. for 6 hours. The reaction was allowed to cool and the crude mixture was applied to a SCX ion exchange cartridge (Varian bond-elute, 10 g) and washed with methanol and then a mixture of 0.880 ammonia:methanol (1:9). The combined basic fractions were reduced in vacuo to afford the title compound (E121). 1H NMR (DMSO-d6) δ 8.56 (1H, dd, J=2.4, 0.4 Hz), 8.48 (1H, br m), 8.20 (1H, dd, J=8.4, 2.4 Hz), 7.16 (1H, d, J=8.0 Hz), 7.03 (1H, dd, J=8.4, 0.4 Hz), 6.91 (1H, d, J=2.4 Hz), 6.86 (1H, dd, J=8.0, 2.4 Hz), 2.87-2.77 (8H, m), 2.36 (4H, m), 2.00 (2H, m), 1.78 (2H, m), 1.58 (2H, m); MS (ES+) m/e 352 [M+H]+.

Workup

  1. temperatureto cool
  2. washwashed with methanol
  3. additiona mixture of 0.880 ammonia:methanol (1:9)

Sources & evidence

ORD record
ord-3295fbbee7244a21bc4b882a67e6c453
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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