Bromoacetic Acid → HCID 11698018, compound

HRID 216187Notes

Reaction equation

HRID 216187 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH2:9][CH2:10][NH:11][C:12]1[N:17]=[C:16]([O:18][CH3:19])[N:15]=[C:14]([C:20]2[CH:21]=[C:22]([CH2:26][OH:27])[CH:23]=[CH:24][CH:25]=2)[CH:13]=1.Br[CH2:29][C:30]([OH:32])=[O:31].[H-].[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH2:9][CH2:10][NH:11][C:12]1[N:17]=[C:16]([O:18][CH3:19])[N:15]=[C:14]([C:20]2[CH:21]=[C:22]([CH:23]=[CH:24][CH:25]=2)[CH2:26][O:27][CH2:29][C:30]([OH:32])=[O:31])[CH:13]=1

Participants

5

Reactant 3

HCID 6227Bromoacetic AcidHCID 24758Sodium hydrideHCID 11668197HCID 11668197, compound

Product 1

HCID 11698018HCID 11698018, compoundYield 530.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-methanol (640 mg, 1.65 mmol) and bromo-acetic acid (0.25 g, 1.82 mmol) in N,N′-dimethylformamide (5 mL) is treated with sodium hydride (60%, 0.28 g, 6.94 mmol) at −30° C. The mixture is allowed to warm to room temperature over 1 hour, stirred for an additional 1 hour and quenched with water. The mixture is diluted with water, and washed with ether. The aqueous phase is acidified to pH 3.8 and the resulting solid is filtered and dried to give (3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzyloxy)-acetic acid [3.9 g, 53%, Example 56]. The filtrate is extracted with ethyl acetate, and the combined extracts are washed with water, dried over magnesium sulfate, and concentrated to afford additional quantity of (3-{6-[2-(2-chloro-6-fluoro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzyloxy)-acetic acid (0.43 g, Example 56). LCMS: RT=2.43 minutes, MS: 446 (M+H). IC50=0.6 nM

Workup

  1. customquenched with water
  2. additionThe mixture is diluted with water
  3. washwashed with ether
  4. filtrationthe resulting solid is filtered
  5. customdried

Sources & evidence

ORD record
ord-5881b8e5b6564710826819a2c07d5312
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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