Potassium Carbonate → Cis-Cyclopentyl[1-(2-amino-6-chloro-4-pyrimidinyl)-6-methyl-3-piperidinyl]carbamate

HRID 2367440Notes

Reaction equation

HRID 2367440 reaction equation
[CH:1]1([O:6][C:7](=[O:16])[NH:8][C@H:9]2[CH2:14][CH2:13][C@@H:12]([CH3:15])[NH:11][CH2:10]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:17][C:18]1[CH:23]=[C:22](Cl)[N:21]=[C:20]([NH2:25])[N:19]=1.C([O-])([O-])=O.[K+].[K+]>C(O)C>[CH:1]1([O:6][C:7](=[O:16])[NH:8][C@H:9]2[CH2:14][CH2:13][C@@H:12]([CH3:15])[N:11]([C:22]3[CH:23]=[C:18]([Cl:17])[N:19]=[C:20]([NH2:25])[N:21]=3)[CH2:10]2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 655222-Amino-4,6-dichloropyrimidine2×HCID 131731329Cis-cyclopentyl[6-methyl-3-piperidinyl]carbamate

Product 1

HCID 131731330Cis-Cyclopentyl[1-(2-amino-6-chloro-4-pyrimidinyl)-6-methyl-3-piperidinyl]carbamateYield 80.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of cis-cyclopentyl[6-methyl-3-piperidinyl]carbamate (107 mg, 0.473 mmol) in ethanol (3 mL) were added 4,6-dichloro-2-pyrimidinamine (116 mg, 0.709 mmol) and K2CO3 (98 mg, 0.709 mmol) in a 5 mL sealable vial. The solution was capped and heated at 100° C. overnight. The reaction was then check with LCMS and was not complete. Additional 4,6-dichloro-2-pyrimidinamine (30 mg) and K2CO3 (50 mg) were added and the resulting mixture was heated overnight. The reaction was concentrated, then 5 mL of DMF were added. Some solids were not soluble. Water (10 mL) was added, and the resulting mixture was extracted 3× with EtOAc. The organics were combined, washed with brine, dried over MgSO4, filtered and concentrated. The clear oil was then purified on Biotage SNAP 10 g column with gradient of 0 to 50% EtOAc in hexane over 30 minutes to afford the title compound (135 mg) as a clear oil. LC-MS (ES) m/z=354 [M+H]+.

Workup

  1. customThe solution was capped
  2. temperaturethe resulting mixture was heated overnight
  3. concentrationThe reaction was concentrated
  4. addition5 mL of DMF were added
  5. additionWater (10 mL) was added
  6. extractionthe resulting mixture was extracted 3× with EtOAc
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe clear oil was then purified on Biotage SNAP 10 g column with gradient of 0 to 50% EtOAc in hexane over 30 minutes

Sources & evidence

ORD record
ord-435c684ecf2644338bfc401ee8ea6712
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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