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

HRID 2043756Notes

Reaction equation

HRID 2043756 reaction equation
[CH2:1]([C:3]1[N:7]([CH2:8][C:9]([OH:11])=O)[N:6]=[C:5]([C:12]([F:15])([F:14])[F:13])[CH:4]=1)[CH3:2].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.Cl.[CH3:35][N:36]([C@H:50]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH2:53][CH2:52][CH2:51]1)[C:37]([C:39]1[N:40]=[C:41]([CH:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)[S:42][CH:43]=1)=[O:38].C(N(CC)CC)C>C(OCC)(=O)C>[CH2:1]([C:3]1[N:7]([CH2:8][C:9]([N:47]2[CH2:48][CH2:49][CH:44]([C:41]3[S:42][CH:43]=[C:39]([C:37]([N:36]([CH3:35])[C@H:50]4[C:59]5[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=5)[CH2:53][CH2:52][CH2:51]4)=[O:38])[N:40]=3)[CH2:45][CH2:46]2)=[O:11])[N:6]=[C:5]([C:12]([F:15])([F:14])[F:13])[CH:4]=1)[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 67463124N-methyl-2-(4-piperidinyl)-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-thiazolecarboxamide monohydrochloride2×HCID 67464323922516-30-12×

Product 1

HCID 667956932-[1-[[5-ethyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-N-methyl-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-thiazolecarboxamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 5-ethyl-3-(trifluoromethyl)-1H-pyrazole-1-acetic acid (170 mg, 0.76 mmol) (i.e. the product of Example 16, Step C) in ethyl acetate (5.0 mL) was treated with 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate, 1.0 mL, 1.6 mmol) and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was added to a stirred suspension of N-methyl-2-(4-piperidinyl)-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-thiazolecarboxamide monohydrochloride (i.e. the product of Example 6 Step C) (219 mg, 0.56 mmol), triethylamine (0.5 mL, 3.75 mmol) in ethyl acetate (5 mL). The reaction mixture was then stirred at room temperature for 12 h. The resulting suspension was concentrated in vacuo and purified by silica gel MPLC using ethyl acetate/hexanes as eluant to give 200 mg of the title product, a compound of the present invention as an oil.

Workup

  1. stirringThe reaction mixture was then stirred at room temperature for 12 h
  2. concentrationThe resulting suspension was concentrated in vacuo
  3. custompurified by silica gel MPLC

Sources & evidence

ORD record
ord-e96ef357d7184f0699fa4e2ab3ddd6c9
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

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