Diisopropylethylamine → 5-Ethyl-2-{4-fluoro-4-[4-(4-methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine

HRID 1869484Notes

Reaction equation

HRID 1869484 reaction equation
Cl.[F:2][C:3]1([C:9]2[S:10][CH:11]=[C:12]([CH2:14][O:15][C:16]3[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=3)[N:13]=2)[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.Cl[C:27]1[N:32]=[CH:31][C:30]([CH2:33][CH3:34])=[CH:29][N:28]=1.CCN(C(C)C)C(C)C>CC(O)C>[CH2:33]([C:30]1[CH:29]=[N:28][C:27]([N:6]2[CH2:5][CH2:4][C:3]([F:2])([C:9]3[S:10][CH:11]=[C:12]([CH2:14][O:15][C:16]4[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=4)[N:13]=3)[CH2:8][CH2:7]2)=[N:32][CH:31]=1)[CH3:34]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 35727632-Chloro-5-ethylpyrimidineHCID 66911042HCID 66911042, compound

Product 1

HCID 250265135-Ethyl-2-{4-fluoro-4-[4-(4-methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 4-fluoro-4-[4-(4-methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidine hydrochloride (4.0 g, 9.01 mmol), 2-chloro-5-ethyl-pyrimidine (1.55 g, 1.2 eq.) and DIPEA (4.7 g, 4 eq.) in 2-propanol (30 mL) in a sealed pressure vessel was stirred at 160° C. (oil bath temperature) overnight. After cooling, the solvent was removed in vacuo. The residue was partitioned between water and EtOAc. The organic phase was washed with brine and dried over Na2SO4. After removal of the solvent, the crude product was purified on silica gel (EtOAc:hexanes=1:1) to afford the desired product as a white solid. 1H NMR (CDCl3): δ 8.19 (2H, s), 7.87 (2H, d, J=9.2 Hz), 7.36 (1H, s), 7.10 (2H, d, J=9.2 Hz), 5.23 (2H, s), 4.69 (2H, m), 3.44 (2H, m), 3.03 (3H, s), 2.48 (2H, q, J=7.6 Hz), 2.15˜2.39 (4H, m), 1.21 (3H, t, J=7.6 Hz).

Workup

  1. temperatureAfter cooling
  2. customthe solvent was removed in vacuo
  3. customThe residue was partitioned between water and EtOAc
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. customAfter removal of the solvent
  7. customthe crude product was purified on silica gel (EtOAc:hexanes=1:1)

Sources & evidence

ORD record
ord-efeb4ed5cdd04cef8247d748b9ca4663
Source dataset
uspto-grants-2009_12
Patent number
US07638541B2

Reaction notes

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