Methylamine → HCID 22315091, compound

HRID 430336Notes

Reaction equation

[CH:1]1([CH2:6][CH:7]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[C:8]([NH:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][N:12]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.[N:35]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:39]2C=CC=CC=2N=N1.CN.O1CCCC1>CN(C)C=O.O>[CH:1]1([CH2:6][CH:7]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[C:8]([NH:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([NH:35][CH3:39])=[O:17])=[CH:13][N:12]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 6-[3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionylamino]-nicotinic acid (prepared in Example 46, 125 mg, 0.31 mmol), N)N-diisopropylethylamine (0.10 mL, 0.61 mmol), and benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (142 mg, 0.32 mmol) in N,N-dimethylformamide (15 mL) at 25° C. was treated dropwise with a 2.0M solution of methylamine in tetrahydrofuran (0.16 mL, 0.32 mmol). The resulting reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was then diluted with water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded 6-[3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionylamino]-N-methyl-nicotinamide (83 mg, 64%) as white solid: mp 229.1-231.7° C.; FAB-HRMS m/e calcd for C21H23Cl2N3O2 (M+H)+420.1245, found 420.1247.

Workup

customThe resulting reaction mixture
extractionextracted with ethyl acetate (3×10 mL)
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-4035788f132a4bd78646c69467b40918
Source dataset: uspto-grants-2001_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06320050B1

Reaction notes

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