2-Amino-2-methyl-1-propanol → 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(2-hydroxy-1,1-dimethyl-ethyl)-nicotinamide

HRID 1514685Notes

Reaction equation

HRID 1514685 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.[NH2:58][C:59]([CH3:63])([CH3:62])[CH2:60][OH:61]>C1COCC1.CO.ClCCl>[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]([NH:58][C:59]([CH3:63])([CH3:62])[CH2:60][OH:61])=[O:20])=[CH:17][N:16]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 118072-Amino-2-methyl-1-propanolHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 667181506-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid

Product 1

HCID 469286656-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(2-hydroxy-1,1-dimethyl-ethyl)-nicotinamideYield 66.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid (200 mg, 0.58 mmol) in THF (6 mL) was added 1-hydroxybenzotriazole hydrate (90.8 mg, 0.58 mmol), N-ethyldiisopropylamine (254 μL, 1.45 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (114 mg, 0.58 mmol) and 2-amino-2-methyl-1-propanol (53.4 mg, 0.58 mmol). The reaction mixture was stirred overnight at room temperature. Chromatography (silica, dichloromethane:methanol=0:100 to 95:5) afforded the title compound (160 mg, 66%) as a colorless oil. MS: m/e=416.2 [M+H]+.

Sources & evidence

ORD record
ord-94b9b274fbc7404fb2f4975602619aac
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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