Benzyl Bromide → Benzyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-vinylpyrimidine-4-carboxylate

HRID 333646Notes

Reaction equation

HRID 333646 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([O:15][CH3:16])[C:9]=2[F:17])[N:5]=[C:4]([C:18]([OH:20])=[O:19])[C:3]=1[CH:21]=[CH2:22].Br[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Li+].[Li+]>CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([O:15][CH3:16])[C:9]=2[F:17])[N:5]=[C:4]([C:18]([O:20][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:19])[C:3]=1[CH:21]=[CH2:22]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11125Lithium CarbonateHCID 468509124-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenylpyrimidine-6-carboxylic acid

Product 1

HCID 70498553Benzyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-vinylpyrimidine-4-carboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-vinylpyrimidine-4-carboxylic acid (prepared by the methods described in U.S. Pat. No. 7,786,044 B2; 0.150 g, 0.463 mmol), (bromomethyl)benzene (0.103 g, 0.602 mmol), and lithium carbonate (Li2CO3; 0.044 g, 0.602 mmol) were combined in DMF (1.5 mL) and heated at 60° C. overnight. The cooled reaction mixture was concentrated and then partitioned between EtOAc and water. The organic phase was dried, concentrated and purified by column chromatography (eluting with an EtOAc/hexanes gradient) to yield benzyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-vinylpyrimidine-4-carboxylate as a white solid (0.154 g, 80%): mp 119-121° C.; 1H NMR (400 MHz, CDCl3) δ 7.67 (dd, J=8.5, 7.5 Hz, 1H), 7.49-7.42 (m, 2H), 7.42-7.32 (m, 3H), 7.21 (dd, J=8.6, 1.7 Hz, 1H), 6.70 (dd, J=17.8, 11.6 Hz, 1H), 5.60 (dd, J=7.7, 1.0 Hz, 1H), 5.57 (s, 1H), 5.39 (s, 2H), 5.35 (s, 2H), 4.00 (d, J=0.8 Hz, 3H); ESIMS m/z 414 ([M+H]+).

Workup

  1. customThe cooled reaction mixture
  2. concentrationwas concentrated
  3. custompartitioned between EtOAc and water
  4. customThe organic phase was dried
  5. concentrationconcentrated
  6. custompurified by column chromatography (
  7. washeluting with an EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-7eccc2f4cd1f4a79b5c58f5b10ba8eeb
Source dataset
uspto-grants-2014_11
Patent number
US08883688B2

Reaction notes

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