Hydrochloric Acid → (E)-6-amino-2-(4-chloro-2,3-difluorophenyl)-5-(2-(trimethylsilyl)vinyl)pyrimidine-4-carboxylic acid

HRID 244312Notes

Reaction equation

HRID 244312 reaction equation
[OH-].[Na+].[NH2:3][C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([F:17])[C:11]=2[F:18])[N:7]=[C:6]([C:19]([O:21]C)=[O:20])[C:5]=1/[CH:23]=[CH:24]/[Si:25]([CH3:28])([CH3:27])[CH3:26].Cl>CO>[NH2:3][C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([F:17])[C:11]=2[F:18])[N:7]=[C:6]([C:19]([OH:21])=[O:20])[C:5]=1/[CH:23]=[CH:24]/[Si:25]([CH3:26])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 70497076(E)-methyl 6-amino-2-(4-chloro-2,3-difluorophenyl)-5-(2-(trimethylsilyl)vinyl)pyrimidine-4-carboxylate

Product 1

HCID 70498582(E)-6-amino-2-(4-chloro-2,3-difluorophenyl)-5-(2-(trimethylsilyl)vinyl)pyrimidine-4-carboxylic acidYield 87%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 2M solution of aqueous sodium hydroxide (400 μL, 0.80 mmol, 2.0 equiv) was added to a stirred suspension of (E)-methyl 6-amino-2-(4-chloro-2,3-difluorophenyl)-5-(2-(trimethylsilyl)vinyl)pyrimidine-4-carboxylate (160 mg, 0.40 mmol, 1.0 equiv) in methanol (4.0 mL) at 23° C. The resulting heterogeneous yellow mixture was stirred at room temperature for 3 h. The reaction mixture was adjusted to approximately pH 4 via dropwise addition of concentrated hydrochloric acid and concentrated under vacuum. The residue was slurried in water and vacuum filtered to afford the title compound as an off-white powder (130 mg, 87%): mp 155-157° C.; 1H NMR (300 MHz, (CD3)2SO) δ 7.77 (m, 1H), 7.51 (m, 1H), 7.31 (br s, 2H); 6.77 (d, J=19 Hz, 1H), 6.30 (d, J=19 Hz, 1H), 0.12 (s, 9H); IR (neat) 3514 (s), 3475 (s), 3407 (s), 3336 (s), 3218 (m), 2963 (m), 1768 (m), 1640 (m), 1612 (m); ESIMS m/z 384 ([M+H]+).

Workup

  1. concentrationconcentrated under vacuum
  2. filtrationvacuum filtered

Sources & evidence

ORD record
ord-f689eaccc4d9493ca7a497db69b3064e
Source dataset
uspto-grants-2014_02
Patent number
US08658568B2

Reaction notes

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