Ammonia → HCID 58169853, compound

HRID 472711Notes

Reaction equation

HRID 472711 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.[NH3:43]>>[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]([NH2:43])=[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

3

Reactant 2

HCID 222AmmoniaHCID 58169863HCID 58169863, compound2×

Product 1

HCID 58169853HCID 58169853, compoundYield 72.5%

Procedure

In a sealed tube a solution of methyl (2R,5S,7R)-8-{[{(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-1,8-diazaspiro[4.5]decane-2-carboxylate (Intermediate 28, 90 mg, 0.149 mmol) in 7M methanolic ammonia (5 ml, 35.0 mmol) was shaken overnight. The solvent was evaporated and the crude was purified by flash-chromatography (Si cartridge 5 g; from 1:0 to 95:5 DCM/MeOH) to give the title compound (63.3 mg, 0.108 mmol, 72.1% yield) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.93 (s, 1H) 7.56 (s, 2H) 7.23-7.31 (m, 1H) 7.14-7.21 (m, 1H) 6.95-7.05 (m, 1H) 6.90 (d, 1H) 6.76 (t, 1H) 5.27-5.43 (m, 1H) 4.14 (d, 1H) 3.41-3.56 (m, 1H) 3.23-3.39 (m, 1H) 2.84 (s, 3H) 2.72 (t, 1H) 2.60-2.68 (m, 1H) 2.32 (s, 3H) 2.06-2.18 (m, 1H) 1.53-1.87 (m, 6H) 1.49 (d, 3H) 1.42 (t, 1H); HPLC: peak @ Rt=4.91 mins; MS: m/z=589 [M+H]+ and 611 [M+Na]+

Workup

  1. customThe solvent was evaporated
  2. customthe crude was purified by flash-chromatography (Si cartridge 5 g; from 1:0 to 95:5 DCM/MeOH)

Sources & evidence

ORD record
ord-1ce874c032e34c1ea6f1a22e5d62af4c
Source dataset
uspto-grants-2014_01
Patent number
US08633214B2

Reaction notes

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