Diisopropylethylamine → 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(1-methyl-1H-pyrazol-4-yl)-nicotinamide

HRID 1514689Notes

Reaction equation

HRID 1514689 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][N:16]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:4][CH:3]=1.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.Cl.CN(C)CCCN=C=NCC.[CH3:58][N:59]1[CH:63]=[C:62]([NH2:64])[CH:61]=[N:60]1>C1COCC1.CCCCCCC.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([NH:64][C:62]4[CH:61]=[N:60][N:59]([CH3:58])[CH:63]=4)=[O:20])=[CH:17][N:16]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 47709901-methyl-1H-pyrazol-4-amineHCID 667181506-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid

Product 1

HCID 469287636-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(1-methyl-1H-pyrazol-4-yl)-nicotinamideYield 57%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

To a solution of 6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid (100 mg, 0.29 mmol) in THF (3 mL) were added 1-hydroxybenzotriazole hydrate (45.3 mg, 0.29 mmol), N-ethyldiisopropylamine (127 μL, 0.73 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (56.7 mg, 0.29 mmol) and 1-methyl-1H-pyrazol-4-ylamine (28.2 mg, 0.29 mmol). The reaction mixture was stirred overnight at room temperature. Chromatography (silica, ethyl acetate:heptane=2:1 to 9:1) afforded the title compound (70 mg, 57%) as a white solid. MS: m/e=424.2 [M+H]+.

Sources & evidence

ORD record
ord-0f896fc12677451bac68c3f8404c5d35
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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