Hydrochloric Acid → 2-{[(4-Fluorophenyl)methyl]oxy}-N-(2-fluoro-3-pyridinyl)-5-(4-morpholinylcarbonyl)benzamide

HRID 1623860Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:10]2[CH:19]=[CH:18][C:17]([C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[O:21])=[CH:16][C:11]=2[C:12](OC)=[O:13])=[CH:4][CH:3]=1.[OH-].[Li+].Cl.C(N(C(C)C)CC)(C)C.[F:40][C:41]1[C:46]([NH2:47])=[CH:45][CH:44]=[CH:43][N:42]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O1CCCC1.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][C:10]2[CH:19]=[CH:18][C:17]([C:20]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)=[O:21])=[CH:16][C:11]=2[C:12]([NH:47][C:46]2[C:41]([F:40])=[N:42][CH:43]=[CH:44][CH:45]=2)=[O:13])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of methyl 2-{[(4-fluorophenyl)methyl]oxy}-5-(4-morpholinylcarbonyl)benzoate (may be prepared as described in Description 109, 93 mg, 0.25 mmol) in tetrahydrofuran (4 ml) was added lithium hydroxide (19 mg, 0.79 mmol) and water (1 ml). The mixture was stirred at 50° C. for one hour, cooled and 2M hydrochloric acid (0.40 ml, 0.80 mmol) was added and the solvent removed in vacuo The residue was redissolved in N,N-dimethylformamide (4 ml) and diisopropylethylamine (0.11 ml, 0.62 mmol), 2-fluoro-3-pyridinamine (36.3 mg, 0.32 mmol) and HATU (284 mg, 0.75 mmol) were added. The solvent was removed in vacuo and the residue purified by MDAP to yield the title compound as an off-white solid. 5 mg.

Workup

temperaturecooled
customthe solvent removed in vacuo The residue
dissolutionwas redissolved in N,N-dimethylformamide (4 ml)
customThe solvent was removed in vacuo
customthe residue purified by MDAP

Sources & evidence

ORD record: ord-5939f64444684457a3094a7c83317634
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08778939B2

Reaction notes

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