Lawesson's reagent → HCID 86658942, compound

HRID 2043778Notes

Reaction equation

HRID 2043778 reaction equation
[CH3:1][N:2]([C@H:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][CH2:31][CH2:30]1)[C:3]([C:5]1[N:6]=[C:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16](=[O:28])[CH2:17][N:18]3[C:22]([CH3:23])=[CH:21][C:20]([C:24]([F:27])([F:26])[F:25])=[N:19]3)[CH2:12][CH2:11]2)[S:8][CH:9]=1)=O.COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:48]2)=CC=1>C1(C)C=CC=CC=1>[CH3:1][N:2]([C@H:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][CH2:31][CH2:30]1)[C:3]([C:5]1[N:6]=[C:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16](=[O:28])[CH2:17][N:18]3[C:22]([CH3:23])=[CH:21][C:20]([C:24]([F:27])([F:26])[F:25])=[N:19]3)[CH2:12][CH2:11]2)[S:8][CH:9]=1)=[S:48]

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 66561986HCID 66561986, compound2×

Product 1

HCID 86658942HCID 86658942, compoundYield 24.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-methyl-2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-thiazolecarboxamide (Compound 149) (273 mg, 0.5 mmol) (i.e. the product of Example 6, Step D) and 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (202 mg, 0.5 mmol) (Lawesson's reagent) in 5 mL of toluene was heated at 100° C. for 3 days. The reaction mixture was concentrated in vacuo, and the resulting residue was dissolved in 10 mL of dichloromethane and washed with 1 M aqueous solution of potassium carbonate, and dried over magnesium sulfate. The filtered residue was concentrated in vacuo and purified by medium-pressure liquid chromatography on silica gel using 50-100% of ethyl acetate in hexanes as eluant to give 70 mg of the title compound, a compound of the present invention as a white foam.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe resulting residue was dissolved in 10 mL of dichloromethane
  3. washwashed with 1 M aqueous solution of potassium carbonate
  4. dry with materialdried over magnesium sulfate
  5. concentrationThe filtered residue was concentrated in vacuo
  6. custompurified by medium-pressure liquid chromatography on silica gel using 50-100% of ethyl acetate in hexanes as eluant

Sources & evidence

ORD record
ord-549f0a0b59c648c48a5649e6d2ecdaeb
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

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