Methanol → 1-(2-{1-[2-(5-Methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-3-phenyl-urea

HRID 1042053Notes

Reaction equation

HRID 1042053 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13](=[O:25])[CH2:14][N:15]3[C:19]([CH3:20])=[CH:18][C:17]([C:21]([F:24])([F:23])[F:22])=[N:16]3)[CH2:9][CH2:8]2)[S:5][CH:6]=1.[C:26]1([N:32]=[C:33]=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CO>C1COCC1>[CH3:20][C:19]1[N:15]([CH2:14][C:13]([N:10]2[CH2:11][CH2:12][CH:7]([C:4]3[S:5][CH:6]=[C:2]([NH:1][C:33]([NH:32][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:34])[N:3]=3)[CH2:8][CH2:9]2)=[O:25])[N:16]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:18]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 7672Phenyl isocyanateHCID 669564011-[4-(4-Amino-thiazol-2-yl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone

Product 1

HCID 669555221-(2-{1-[2-(5-Methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-3-phenyl-urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-[4-(4-amino-thiazol-2-yl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone (100 mg, 0.27 mmol) in THF (5 mL) is added dropwise a solution of phenylisocyanate (30 μL, 0.28 mmol) in THF (1 mL) at 0° C. After stirring overnight at RT, methanol (1 mL) is added to the reaction mixture. After stirring 15 min. at RT, the solvents are evaporated and the residue was triturated with diethylether (5 mL) to induce precipitation. The resulting solid is filtered and dried under vacuum to give 1-(2-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-3-phenyl-urea as beige solid (Compound No. I.g.024, 105 mg, 79%). M.p.=192.6° C. 1H-NMR (400 MHz, CDCl3): δ=1H-NMR (MeOD): d=1.65 (m, 1H), 1.80 (m, 1H), 2.40 (m, 2H), 2.30 (s, 3H), 2.98 (m, 1H), 3.30 (m, 1H), 3.39 (m, 1H), 4.10 (m, 1H), 4.52 (m, 1H), 5.22 (2d, 2H, diastereotopic), 6.42 (s, 1H), 7.05 (t, 1H), 7.09 (s, 1H), 7.26-7.45 (m, 6H). MS: m/z=494 (M+1).

Workup

  1. stirringAfter stirring 15 min. at RT
  2. customthe solvents are evaporated
  3. customthe residue was triturated with diethylether (5 mL)
  4. customprecipitation
  5. filtrationThe resulting solid is filtered
  6. customdried under vacuum

Sources & evidence

ORD record
ord-e2de56319d7548a8881095eb5e9de008
Source dataset
uspto-grants-2013_10
Patent number
US08557821B2

Reaction notes

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