Potassium Carbonate → 4-Chloro-2-cyclopropyl-6-(3-fluoro-azetidin-1-yl)-pyrimidine

HRID 1984310Notes

Reaction equation

HRID 1984310 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([CH:9]2[CH2:11][CH2:10]2)[N:3]=1.Cl.[F:13][CH:14]1[CH2:17][NH:16][CH2:15]1.C(=O)([O-])[O-].[K+].[K+]>COCC(O)C>[Cl:8][C:6]1[CH:7]=[C:2]([N:16]2[CH2:17][CH:14]([F:13])[CH2:15]2)[N:3]=[C:4]([CH:9]2[CH2:11][CH2:10]2)[N:5]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 101250543-fluoroazetidine HydrochlorideHCID 249036874,6-Dichloro-2-cyclopropylpyrimidine

Product 1

HCID 101491454-Chloro-2-cyclopropyl-6-(3-fluoro-azetidin-1-yl)-pyrimidineYield 92.6%

Reagents, catalysts & solvents 1

HCID 79001-Methoxy-2-propanolSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 4,6-dichloro-2-cyclopropylpyrimidine 19 (1.05 g, 5.5 mmol), 3-fluoroazetidine hydrochloride 162 (0.68 g, 6 mmol) and potassium carbonate (2.48 g, 18 mmol) in 1-methoxy-2-propanol (10 ml) is heated at 65° C. for 2 hours. The mitre is cooled, concentrated in vacuo, diluted with dichloromethane and washed three times with water. The combined organic layers are dried over magnesium sulfate and concentrated in vacuo to afford 4-chloro-2-cyclopropyl-6-(3-fluoro-azetidin-1-yl)-pyrimidine 163 (1.16 g, 92%) as a yellow oil which is used in the next step without further purification.

Workup

  1. temperatureThe mitre is cooled
  2. concentrationconcentrated in vacuo
  3. additiondiluted with dichloromethane
  4. washwashed three times with water
  5. dry with materialThe combined organic layers are dried over magnesium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d748d46600664003a6b506f0638c3878
Source dataset
uspto-grants-2009_06
Patent number
US07544675B2

Reaction notes

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