Triethylamine → N-methyl-2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-4-thiazolecarboxamide

HRID 1966950Notes

Reaction equation

HRID 1966950 reaction equation
[CH3:1][NH:2][CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][CH2:4]1.C(N(CC)CC)C.[CH3:20][C:21]1[N:25]([CH2:26][C:27]([N:29]2[CH2:34][CH2:33][CH:32]([C:35]3[S:36][CH:37]=[C:38]([C:40](Cl)=[O:41])[N:39]=3)[CH2:31][CH2:30]2)=[O:28])[N:24]=[C:23]([C:43]([F:46])([F:45])[F:44])[CH:22]=1>ClCCl>[CH3:1][N:2]([CH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][CH2:4]1)[C:40]([C:38]1[N:39]=[C:35]([CH:32]2[CH2:33][CH2:34][N:29]([C:27](=[O:28])[CH2:26][N:25]3[C:21]([CH3:20])=[CH:22][C:23]([C:43]([F:44])([F:46])[F:45])=[N:24]3)[CH2:30][CH2:31]2)[S:36][CH:37]=1)=[O:41]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 46475N-methyl-1,2,3,4-tetrahydronaphthalen-1-amineHCID 866377272-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarbonyl chloride2×

Product 1

HCID 58242735N-methyl-2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-4-thiazolecarboxamideYield 59.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (145 mg, 0.9 mmol) and triethylamine (0.16 mL, 1.13 mmol) in dichloromethane (2 mL) at 0° C. was gradually added 2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarbonyl chloride (316 mg, 0.75 mmol) (i.e. the product of Example 2, Step D). The reaction mixture was stirred at room temperature for 16 h and then diluted with dichloromethane (4 mL). The mixture was washed with water, 1 N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and brine, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo to provide crude product, which was purified by medium-pressure liquid chromatography on silica gel using 60-100% of ethyl acetate in hexanes as eluant to give 242 mg of the title compound as white foam.

Workup

  1. customat 0° C.
  2. washThe mixture was washed with water, 1 N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customto provide crude product, which
  7. customwas purified by medium-pressure liquid chromatography on silica gel using 60-100% of ethyl acetate in hexanes as eluant

Sources & evidence

ORD record
ord-4c2778f235164072b98c545f0e56e317
Source dataset
uspto-grants-2013_04
Patent number
US08420673B2

Reaction notes

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