Ammonia methanol → HCID 59596712, compound

HRID 2264844Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([C@@H:18]2[NH:22][C@H:21]([C:23]([O:25]C)=O)[CH2:20][CH2:19]2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17])#[N:2].[NH3:27].CO>>[C:1]([C:3]1[CH:4]=[C:5]([C@@H:18]2[NH:22][C@H:21]([C:23]([NH2:27])=[O:25])[CH2:20][CH2:19]2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17])#[N:2]

Participants

Reactant 2

HCID 21705897Ammonia methanol

HCID 59596666HCID 59596666, compound

Product 1

HCID 59596712HCID 59596712, compoundYield 72%

Procedure

A solution of methyl (5R)-5-(3-cyano-4-{[(2-fluorophenyl)methyl]oxy}phenyl)-L-prolinate (D73, 64 mg, 0.180 mmol) in 7M NH3/MeOH (2 ml) was stirred 10.5 h at 40° C. The solvent was evaporated and the residue purified via flash chromatography using a DCM/MeOH (98:2 to 8:2) to afford (5R)-5-(3-cyano-4-{[(2-fluorophenyl)methyl]oxy}phenyl)-L-prolinamide (44 mg, 72%) as the free base. The title compound (32 mg) was prepared as described for example 4 in procedure 2. MS: (ES/+) m/z: 340 [MH+], C19H18FN3O2 requires 339. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.37 (br. s., 1H), 8.54 (br. s., 1H), 8.04 (br. s., 1H), 7.97 (dd, 1H), 7.85 (dd, 1H), 7.74 (br. s., 1H), 7.63 (td, 1H), 7.50 (d, 1H), 7.43-7.55 (m, 1H), 7.25-7.36 (m, 2H), 5.32-5.44 (m, 2H), 4.56-4.82 (m, 1H), 4.21-4.42 (m, 1H), 2.22-2.43 (m, 2H), 1.94-2.26 (m, 2H).

Workup

customThe solvent was evaporated
customthe residue purified via flash chromatography

Sources & evidence

ORD record: ord-d6e8be68cb864fa69383264eb8401360
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07855218B2

Reaction notes

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