Ammonia → HCID 44251422, compound

HRID 384033Notes

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

Reactant 3

HCID 222Ammonia

HCID 887Methanol

HCID 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, 2 H) 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).

Workup

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

Sources & evidence

ORD record: ord-c43693f2dd064645b140b3a413c59223
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367692B2

Reaction notes

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