4-Amino-6-chloropyrimidine → 1-(6-Aminopyrimidin-4-yl)azetidin-3-ol

HRID 2366214Notes

Reaction equation

HRID 2366214 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([OH:6])[CH2:3]1.Cl[C:8]1[N:13]=[CH:12][N:11]=[C:10]([NH2:14])[CH:9]=1>CO.O>[NH2:14][C:10]1[N:11]=[CH:12][N:13]=[C:8]([N:2]2[CH2:5][CH:4]([OH:6])[CH2:3]2)[CH:9]=1

Participants

5

Reactant 2

HCID 2380124-Amino-6-chloropyrimidineHCID 27592903-Hydroxyazetidine hydrochloride

Product 1

HCID 668014651-(6-Aminopyrimidin-4-yl)azetidin-3-olYield 85%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of 3-azetidinol hydrochloride (454 mg, 4.1 mmol) in MeOH and water was loaded onto an Isolute® SCX-2 cartridge that was washed with MeOH and the product eluted with 2M ammonia in MeOH. The relevant fractions were concentrated to dryness under reduced pressure. The resultant residue was then added to a solution of 6-chloro-pyrimidin-4-ylamine (151 mg, 1.16 mmol) in IMS (10 mL) under argon and heated under reflux for 18 hours. The reaction mixture was cooled and then loaded onto an Isolute® SCX-2 column. The column was then washed with MeOH and eluted with 2 M ammonia in MeOH. The relevant fractions were concentrated to dryness under reduced pressure and the resulting residue was purified by flash chromatography (NH2 cartridge, 0-5% MeOH in DCM) to give the desired compound as a white solid (163 mg, 85% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.90 (d, J=1.0 Hz, 1H), 6.18 (s, 2H), 5.65 (d, J=6.5 Hz, 1H), 5.21 (d, J=1.1 Hz, 1H), 4.54-4.53 (m, 1H), 4.07 (dd, J=8.7, 6.7 Hz, 2H), 3.59 (dd, J=8.8, 4.6 Hz, 2H).

Workup

  1. washwas washed with MeOH
  2. washthe product eluted with 2M ammonia in MeOH
  3. concentrationThe relevant fractions were concentrated to dryness under reduced pressure
  4. temperatureheated
  5. temperatureunder reflux for 18 hours
  6. temperatureThe reaction mixture was cooled
  7. washThe column was then washed with MeOH
  8. washeluted with 2 M ammonia in MeOH
  9. concentrationThe relevant fractions were concentrated to dryness under reduced pressure
  10. customthe resulting residue was purified by flash chromatography (NH2 cartridge, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-833787938acc4aac836c6c2be33a5677
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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