Diisopropylethylamine → HCID 57986802, compound

HRID 871927Notes

Reaction equation

HRID 871927 reaction equation
Cl.[F:2][C:3]1([C:9]2[S:10][C:11]([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)=[CH:12][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][C:11]([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)=[CH:12][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 66911027HCID 66911027, compound

Product 1

HCID 57986802HCID 57986802, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 4-fluoro-4-[5-(4-methanesulfonyl-phenoxymethyl)-thiazol-2-yl]-piperidine hydrochloride (1.2 g, 2.76 mmol), 2-chloro-5-ethyl-pyrimidine (425 mg, 1.1 eq.) and DIPEA (1.4 g, 4 eq.) in 2-propanol (20 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), 7.90 (2H, d, J=8.8 Hz), 7.73 (1H, d), 7.10 (2H, d, J=8.8 Hz), 5.31 (2H, s), 4.67 (2H, m), 3.44 (2H, m), 3.04 (3H, s), 2.48 (2H, q, J=7.6 Hz), 2.13˜2.38 (4H, m), 1.20 (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-7af9b5f860d5408db8ee1feeecdd2c50
Source dataset
uspto-grants-2015_03
Patent number
US08975258B2

Reaction notes

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