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

HRID 2043748Notes

Reaction equation

HRID 2043748 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]([CH2:12][C:13]([OH:15])=O)[N:4]=1.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.Cl.[CH3:37][N:38]([C@H:52]1[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH2:55][CH2:54][CH2:53]1)[C:39]([C:41]1[N:42]=[C:43]([CH:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)[S:44][CH:45]=1)=[O:40].C(N(CC)CC)C>C(OCC)(=O)C>[F:16][C:2]([F:1])([F:17])[C:3]1[CH:7]=[C:6]([C:8]([F:9])([F:10])[F:11])[N:5]([CH2:12][C:13]([N:49]2[CH2:50][CH2:51][CH:46]([C:43]3[S:44][CH:45]=[C:41]([C:39]([N:38]([CH3:37])[C@H:52]4[C:61]5[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=5)[CH2:55][CH2:54][CH2:53]4)=[O:40])[N:42]=3)[CH2:47][CH2:48]2)=[O:15])[N:4]=1

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 86647452HCID 86647452, compound2×

Product 1

HCID 866589402-[1-[[3,5-bis(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 3,5-bis-(trifluoromethyl)-1H-pyrazole-1-acetic acid (190 mg, 0.73 mmol) (i.e. the product of Example 14, Step A) 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) (210 mg, 0.53 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 MPLC on silica gel using ethyl acetate/hexanes as eluant to give 110 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 MPLC on silica gel

Sources & evidence

ORD record
ord-504a755b1df84935a0459405b222c470
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

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