Triethylamine → HCID 86712657, compound

HRID 1778998Notes

Reaction equation

HRID 1778998 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.ClCCCl.CC(O)(C)C.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]2)=[C:25]([CH3:42])[CH:24]=1.CCN(CC)CC>CO.[Cl-].[Zn+2].[Cl-]>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])[CH2:31][CH2:30]3)=[C:25]([CH3:42])[CH:24]=2)[N:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 21868497Tert-butyl alcohol 1,2-dichloroethane3×HCID 58166533955369-50-3

Product 1

HCID 86712657HCID 86712657, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Zinc(II) chloride (1.0 M in Et2O; 0.661 mL, 0.661 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (0.132 g, 0.606 mmol) in 1:1 DCE/t-BuOH (5 mL) at 0° C. under nitrogen. The resulting mixture was stirred for 1 hour at 0° C. then tert-butyl 4-(4-amino-2-methylphenyl)piperidine-1-carboxylate (A39) (0.160 g, 0.551 mmol) in 1:1 DCE/t-BuOH (5 mL) was added. A solution of Et3N (840 μL, 0.606 mmol) in 1:1 DCE/t-BuOH (5 mL) at 0° C. was then added and the resulting mixture was vigorously stirred for a further 30 minutes at 0° C. then at room temperature for 16 hours. The volatiles were removed in vacuo to afford a brown residue which was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.) to yield a pale yellow solid. The solid was suspended in MeOH (10 mL) and water (10 mL) and the resulting suspension filtered to give the title compound A40 as a white solid (0.231 g, 89%); 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 7.35 (d, J=8.2 Hz, 1H), 7.27 (brs, 1H), 7.24 (d, J=2.3 Hz, 1H), 7.11 (d, J=8.4 Hz, 1H), 4.32-4.04 (m, 2H), 2.79-2.73 (m, 3H), 2.30 (s, 3H), 1.67 (d, J=13.0 Hz, 2H), 1.62-1.45 (m, obscured), 1.42 (s, 9H). LCMS-A: rt 6.895 min; m/z 469.1 [M−H]−.

Workup

  1. stirringthe resulting mixture was vigorously stirred for a further 30 minutes at 0° C.
  2. waitat room temperature for 16 hours
  3. customThe volatiles were removed in vacuo
  4. customto afford a brown residue which
  5. customwas purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.)
  6. customto yield a pale yellow solid
  7. filtrationwater (10 mL) and the resulting suspension filtered

Sources & evidence

ORD record
ord-dc2119e8a5434b1eb3ae6a72028169ec
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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