Diisopropylethylamine → 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-((R)-1-hydroxymethyl-propyl)-nicotinamide

HRID 1514687Notes

Reaction equation

HRID 1514687 reaction equation
O.[OH:2][C:3]1[C:11]2[N:10]=NN[C:7]=2[CH:6]=CC=1.C(N(C(C)C)C(C)C)C.Cl.CN(C)CCCN=C=NCC.[F:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[C:44]([CH2:45][O:46][C:47]3[CH:55]=[CH:54][C:50]([C:51]([OH:53])=O)=[CH:49][N:48]=3)=[C:43]([CH2:56][OH:57])[O:42][N:41]=2)=[CH:36][CH:35]=1.N[C@H](CC)CO>C1COCC1>[F:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[C:44]([CH2:45][O:46][C:47]3[CH:55]=[CH:54][C:50]([C:51]([NH:10][C@@H:11]([CH2:3][OH:2])[CH2:7][CH3:6])=[O:53])=[CH:49][N:48]=3)=[C:43]([CH2:56][OH:57])[O:42][N:41]=2)=[CH:36][CH:35]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27238562-Amino-1-butanol, (-)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 667181506-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acidHCID 178526939HCID 178526939, compound

Product 1

HCID 469286676-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-((R)-1-hydroxymethyl-propyl)-nicotinamideYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Hydroxybenzotriazole hydrate (45.3 mg, 0.29 mmol), N-ethyldiisopropylamine (253 μL, 1.45 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (56.7 mg, 0.29 mmol) were added at 0° C. to a solution of 6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid (100 mg, 0.29 mmol) and (R)-(−)-2-amino-1-butanol (34.0 μL, 0.35 mmol) in THF (8 mL). The reaction mixture was stirred at room temperature overnight. Extraction with 1 N aqueous hydrochloric acid/ethyl acetate and chromatography (silica, ethyl acetate:heptane=1:1 to 100:0) afforded the title compound (60 mg, 50%) as a white solid. MS: m/e=414.2 [M−H]−.

Workup

  1. extractionExtraction with 1 N aqueous hydrochloric acid/ethyl acetate and chromatography (silica, ethyl acetate:heptane=1:1 to 100:0)

Sources & evidence

ORD record
ord-6e32430496f74f88b082ecaf220d6284
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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