Water → 2,4-dichloro-N-(2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrimidin-5-amine

HRID 2386271Notes

Reaction equation

HRID 2386271 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([NH:9][CH2:10][C:11]([CH3:14])([OH:13])[CH3:12])=[CH:4][N:3]=1.[O:15]1[CH:20]=[CH:19][CH2:18][CH2:17][CH2:16]1.O>ClCCl.CC1C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([NH:9][CH2:10][C:11]([CH3:14])([O:13][CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][O:15]2)[CH3:12])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 80803,4-dihydro-2H-pyranHCID 866515891-(2,4-Dichloropyrimidin-5-ylamino)-2-methylpropan-2-ol

Product 1

HCID 866515902,4-dichloro-N-(2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrimidin-5-amineYield 90.1%

Reagents, catalysts & solvents 2

HCID 161440Pyridine 4-methylbenzene-1-sulfonateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-(2,4-dichloropyrimidin-5-ylamino)-2-methylpropan-2-ol (258 mg, 1.09 mmol) and 3,4-dihydro-2H-pyran (0.200 ml, 2.18 mmol) in dichloromethane (7 ml) was added pyridine 4-methylbenzenesulfonate (13.7 mg, 0.055 mmol) and the reaction mixture was stirred for 16 hours. The reaction mixture was poured into water and extracted with Et2O. The organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a crude oil. The crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 100:0 to 3:1) to afford 2,4-dichloro-N-(2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrimidin-5-amine (315 mg, 0.982 mmol, 90% yield) as a pale yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.18 (s, 3H) 1.23 (s, 3H) 1.25-1.75 (m, 6H) 3.27-3.32 (m, 2H) 3.37-3.49 (m, 1H) 3.69-3.83 (m, 1H) 4.74-4.86 (m, 1H) 5.75 (t, J=6.32 Hz, 1H) 8.36 (s, 1H).

Workup

  1. extractionextracted with Et2O
  2. dry with materialThe organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a crude oil
  6. customThe crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 100:0 to 3:1)

Sources & evidence

ORD record
ord-83fc0e7b7e6f4a2b84e2b01b8a8c4dc1
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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