Ammonia → HCID 44251422, compound

HRID 472703Notes

Reaction equation

HRID 472703 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]([N:15]([CH3:40])[C:16]([N:18]2[CH2:31][CH2:30][C@:21]3([NH:25][C@@H:24]([C:26]([O:28]C)=O)[CH2:23][CH2:22]3)[CH2:20][C@@H:19]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[CH3:39])=[O:17])[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CO.[NH3:45]>>[F:10][C:9]([F:12])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]([N:15]([CH3:40])[C:16]([N:18]2[CH2:31][CH2:30][C@:21]3([NH:25][C@@H:24]([C:26]([NH2:45])=[O:28])[CH2:23][CH2:22]3)[CH2:20][C@@H:19]2[C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[CH3:39])=[O:17])[CH3:14])[CH:4]=[C:3]([C:2]([F:1])([F:41])[F:42])[CH:8]=1

Participants

4

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 58169887HCID 58169887, compound2×

Product 1

HCID 44251422HCID 44251422, compound

Procedure

In a sealed tube a solution of Methyl (2R, 5S,7R)-8-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-1,8-diazaspiro[4.5]decane-2-carboxylate (Intermediate 12, 21.6 mg, 0.036 mmol) in 7N Ammonia in MeOH (5 mL, 35.0 mmol) was stirred at 25° C. for 1 day. The solvent was evaporated to dryness and the crude was purified by silica cartridge (2 g) (at first EtOAc and then 97.5:2.5 DCM/0.5 M NH3 in MeOH) to give 17.8 mg of the title compound as a white foam. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.00 (s, 1H) 7.70 (s, 2H) 7.28 (d, 1H) 7.15 (dd, 1H) 7.03 (d, 1H) 6.92 (dd, 1H) 6.78 (t, 1H) 5.31 (q, 1H) 4.14 (dd, 1H) 3.47 (t, 1H) 3.27-3.38 (m, 1H) 2.75 (s, 3H) 2.76 (t, 1H) 2.32 (s, 3H) 2.05-2.15 (m, 1H) 1.68-1.85 (m, 3H) 1.52-1.68 (m, 3H) 1.47 (d, 3H) 1.39-1.54 (m, 1H). NMR analysis revealed the presence of a large amount of DCM (˜55% w/w). HPLC: Rt 4.90 mins. This batch was used directly in the next step.

Workup

  1. customThe solvent was evaporated to dryness
  2. customthe crude was purified by silica cartridge (2 g) (at first EtOAc

Sources & evidence

ORD record
ord-a46526fb2a9e4b439238921bffc79c17
Source dataset
uspto-grants-2014_01
Patent number
US08633214B2

Reaction notes

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