Dimethylamine → 4-(2-Fluoro-4-hydroxymethyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

HRID 1177100Notes

Reaction equation

HRID 1177100 reaction equation
[CH3:1][NH:2][CH3:3].[BH3-]C#N.[Na+].[CH3:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH:27]=[C:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([CH:35]=[O:36])=[CH:31][C:30]=3[F:37])[C:20]3[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=3[CH:18]=2)=[O:16])=[N:10]1>CO>[CH3:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH:27]=[C:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([CH2:35][N:2]([CH3:3])[CH3:1])=[CH:31][C:30]=3[F:37])[C:20]3[CH2:21][C:22]([CH3:24])([CH3:25])[O:23][C:19]=3[CH:18]=2)=[O:16])=[N:10]1.[CH3:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH:27]=[C:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([CH2:35][OH:36])=[CH:31][C:30]=3[F:37])[C:20]3[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=3[CH:18]=2)=[O:16])=[N:10]1

Participants

6

Reactant 3

HCID 674Dimethylamine2×HCID 5003444Sodium cyanoborohydride2×HCID 595600834-(2-fluoro-4-formyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

Product 2

HCID 595600364-(4-dimethylaminomethyl-2-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid(1-methyl-1H-pyrazol-3-yl)-amideYield 24%HCID 595602584-(2-Fluoro-4-hydroxymethyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amideYield 25%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To dimethylamine (0.6 mL, 2.0 M, 1.0 mmol) in MeOH (5 mL) was added NaCNBH3 (31 mg, 0.49 mmol). The mixture was heated to 50° C. for 1 hr, and then 4-(2-fluoro-4-formyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (39a) (100 mg, 0.24 mmol) was added. The reaction mixture was heated to 50° C. for 1 hr. Additional NaCNBH3 (31 mg, 0.49 mmol) and dimethylamine (0.3 mL, 2.0 M, 0.5 mmol) were added to the reaction mixture. The mixture was heated at 50° C. for 1 hr, then concentrated and purified by reverse phase chromatograph to give 4-(4-dimethylaminomethyl-2-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (26 mg, 24% yield) and 4-(2-Fluoro-4-hydroxymethyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (25 mg, 25% yield) as white solid.

Workup

  1. temperatureThe reaction mixture was heated to 50° C. for 1 hr
  2. temperatureThe mixture was heated at 50° C. for 1 hr
  3. concentrationconcentrated
  4. custompurified by reverse phase chromatograph

Sources & evidence

ORD record
ord-e4dba46d89ab48abaf96588108104844
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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