2-Fluoro-3-methoxyphenylboronic acid → 3-[2(R)-tert-butoxycarbonylamino-2-cyclohexylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione

HRID 2054523Notes

Reaction equation

HRID 2054523 reaction equation
Br[C:2]1[C:3](=[O:35])[N:4]([CH2:19][C@H:20]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[C:5](=[O:18])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:7]=1[CH3:8].[F:36][C:37]1[C:42]([O:43][CH3:44])=[CH:41][CH:40]=[CH:39][C:38]=1B(O)O>CCO.COCCOC>[C:31]([O:30][C:28]([NH:27][C@H:20]([CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[CH2:19][N:4]1[C:3](=[O:35])[C:2]([C:38]2[CH:39]=[CH:40][CH:41]=[C:42]([O:43][CH3:44])[C:37]=2[F:36])=[C:7]([CH3:8])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:5]1=[O:18])=[O:29])([CH3:34])([CH3:33])[CH3:32]

Participants

4

Reactant 2

HCID 49857442-Fluoro-3-methoxyphenylboronic acidHCID 210184025-bromo-3-[2(R)-tert-butoxycarbonylamino-2-cyclohexylethyl]-1-[2,6-difluorobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 589650063-[2(R)-tert-butoxycarbonylamino-2-cyclohexylethyl]-5-(2-fluoro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dioneYield 32.3%

Reagents, catalysts & solvents 1

HCID 20074477Dimethoxyethane ethanolSolvent

Conditions

Temperature
80 °C

Procedure

5-Bromo-3-[2(R)-tert-butoxycarbonylamino-2-cyclohexylethyl]-1-[2,6-difluorobenzyl]-6-methyl-pyrimidine-2,4(1H,3H)-dione 2b (1.0 g, 1.79 mmol) in bezene/EtOH/ethylene glycol dimethyl ether (20/2/22 mL) was added 2-fluoro-3-methoxyphenylboronic acid (382 mg, 2.24 mmol) and saturated Ba(OH)2/water (˜0.5 M, 15 mL). The reaction mixture was deoxygenated with N2 for 10 minutes, tetrakis(triphenylphosine) palladium (0) (208 mg, 0.18 mmol) was added and the reaction mixture was heated at 80° C. overnight under N2. The reaction mixture was partitioned between brine and EtOAc. The organic layer was dried (sodium sulfate), evaporated, and purified by flash chromatography (silica, 30% EtOAc/hexanes) to give compound 2c (348 mg, 32.3%). MS (CI) m/z 502.20 (MH+-Boc).

Workup

  1. customThe reaction mixture was deoxygenated with N2 for 10 minutes
  2. customThe reaction mixture was partitioned between brine and EtOAc
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. customevaporated
  5. custompurified by flash chromatography (silica, 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-da5ef2d7a6f2438895703209094e96d5
Source dataset
uspto-grants-2008_02
Patent number
US07329669B2

Reaction notes

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