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

HRID 1516501Notes

Reaction equation

HRID 1516501 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-c4de5e885f954e15a68cd77c92bae5f6
Source dataset
uspto-grants-2012_07
Patent number
US08227495B2

Reaction notes

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