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

HRID 2043752
Notes
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Reaction equation

HRID 2043752 reaction equation
[CH2:1]([C:3]1[CH:7]=[C:6]([CH2:8][CH3:9])[N:5]([CH2:10][C:11]([OH:13])=O)[N:4]=1)[CH3:2].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.Cl.[CH3:33][N:34]([C@H:48]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH2:51][CH2:50][CH2:49]1)[C:35]([C:37]1[N:38]=[C:39]([CH:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)[S:40][CH:41]=1)=[O:36].C(N(CC)CC)C>C(OCC)(=O)C>[CH2:1]([C:3]1[CH:7]=[C:6]([CH2:8][CH3:9])[N:5]([CH2:10][C:11]([N:45]2[CH2:46][CH2:47][CH:42]([C:39]3[S:40][CH:41]=[C:37]([C:35]([N:34]([CH3:33])[C@H:48]4[C:57]5[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=5)[CH2:51][CH2:50][CH2:49]4)=[O:36])[N:38]=3)[CH2:43][CH2:44]2)=[O:13])[N:4]=1)[CH3:2]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 67464828HCID 67464828, compound2×

Product 1

HCID 67463009
2-[1-[(3,5-diethyl-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-diethyl-1H-pyrazol-1-acetic acid (135 mg, 0.74 mmol) (i.e. the product of Example 15, 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) (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 60 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-43a097585d444883b74265528e0d5bd7
Source dataset
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08586611B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes