2-Amino-4,6-dichloropyrimidine → 4-Chloro-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-2-pyrimidinamine

HRID 2367279Notes

Reaction equation

HRID 2367279 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[N:3]=1.[F:10][C:11]([F:18])([F:17])[CH:12]1[CH2:16][CH2:15][CH2:14][NH:13]1.CCN(C(C)C)C(C)C>CC#N>[Cl:8][C:6]1[CH:5]=[C:4]([N:13]2[CH2:14][CH2:15][CH2:16][CH:12]2[C:11]([F:18])([F:17])[F:10])[N:3]=[C:2]([NH2:1])[N:7]=1

Participants

5

Reactant 3

HCID 655222-Amino-4,6-dichloropyrimidineHCID 81531DiisopropylethylamineHCID 27828392-(Trifluoromethyl)pyrrolidine

Product 1

HCID 585047924-Chloro-6-[2-(trifluoromethyl)-1-pyrrolidinyl]-2-pyrimidinamineYield 36.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-Amino-4,6-dichloropyrimidine (143 mg, 0.870 mmol) was added to a stirring mixture of 2-trifluoromethylpyrrolidine (121 mg, 0.870 mmol) and Hunig's base (0.23 mL, 1.31 mmol) in CH3CN (2.5 mL) in a microwave vessel. The reaction was capped and heated in a microwave reactor for 1 hour. Silica gel chromatography (Analogix RS-12 g cartridge) eluting with 5-10% EtOAc—CHCl3 gave the title compound (85 mg) as a white solid. 1H NMR (400 MHz, CDCl3, * denotes minor rotamer): δ 1.96-2.15 (m, 2H), 2.15-2.32 (m, 2H), 3.37-3.52 (m, 1H), 3.54-3.65 (m, 1H), 4.82, 5.60* (bs, 1H), 5.00 (bs, 2H), 5.94, 6.72* (s, 1H).

Workup

  1. customThe reaction was capped
  2. temperatureheated in a microwave reactor for 1 hour
  3. washSilica gel chromatography (Analogix RS-12 g cartridge) eluting with 5-10% EtOAc—CHCl3

Sources & evidence

ORD record
ord-78de93db0a6a4e07b824e260fd806077
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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