Triethylamine → HCID 86712681, compound

HRID 1779033Notes

Reaction equation

HRID 1779033 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:31]=[CH:30][C:17]([CH2:18][N:19]([CH2:27][CH2:28][OH:29])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:16][CH:15]=1.CCN(CC)CC>[Cl-].[Zn+2].[Cl-].ClCCCl.CC(O)(C)C>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([CH2:18][N:19]([CH2:27][CH2:28][OH:29])[C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[CH:30][CH:31]=2)[N:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 86712680HCID 86712680, compound

Product 1

HCID 86712681HCID 86712681, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 21868497Tert-butyl alcohol 1,2-dichloroethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

Zinc(II) chloride (1.0 M in Et2O; 3.30 mL, 3.30 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (0.658 g, 3.03 mmol) in 1:1 DCE/t-BuOH (20 mL) at 0° C. under nitrogen. After stirring for 1 hour at 0° C., a solution of tert-butyl 4-aminobenzyl(2-hydroxyethyl)carbamate (A70) (0.734 g, 2.75 mmol) in 1:1 DCE/t-BuOH (20 mL) was added followed by a solution of Et3N (0.423 mL, 3.03 mmol) in 1:1 DCE/t-BuOH (5 mL) at 0° C. The resulting mixture was vigorously stirred at 0° C. for 30 minutes, then at room temperature for 20 hours. The volatiles were evaporated in vacuo and the residue adsorbed onto silica gel then purified by column chromatography (CombiFlash Rf, 80 g SiO2 cartridge, 10-40% EtOAc in cyclohexane) to give the title compound A71 as a white solid (1.06 g, 85%); 1H NMR (300 MHz, CDCl3) δ 8.60 (s, 1H), 7.59-7.52 (m, 3H), 7.28 (m, 2H), 4.49 (s, 2H), 3.74 (s, 2H), 3.43-3.20 (m, 3H), 1.50 (s, 9H). LCMS-B: rt 7.856 min; m/z 447 [M+H]+.

Workup

  1. stirringThe resulting mixture was vigorously stirred at 0° C. for 30 minutes
  2. waitat room temperature for 20 hours
  3. customThe volatiles were evaporated in vacuo
  4. customthen purified by column chromatography (CombiFlash Rf, 80 g SiO2 cartridge, 10-40% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-17180c2751c54623bcae7bfa80ab02f7
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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