2-Chlorobenzoyl chloride → HCID 68062335, compound

HRID 1524247Notes

Reaction equation

HRID 1524247 reaction equation
[NH2:1][C:2]1[S:6][C:5]([C:7]2[N:11]([CH3:12])[N:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)=[N:4][CH:3]=1.[Cl:17][C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20](Cl)=[O:21].CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:17][C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20]([NH:1][C:2]1[S:6][C:5]([C:7]2[N:11]([CH3:12])[N:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)=[N:4][CH:3]=1)=[O:21]

Participants

6

Reactant 3

HCID 691102-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 667789175-Amino-2-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]-1,3-thiazole

Product 1

HCID 68062335HCID 68062335, compoundYield 31.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 5-amino-2-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl]-1,3-thiazole (66, 8.1 mg, 0.03 mmol) in 1 ml DCM were added 2-chlorobenzoyl chloride (3.8 μl, 2 eq), DIEA (52 μl, 3 eq) and DMAP (2 mg). After stirred at r.t for 2 h, the reaction mixture was worked up with DCM/aq. NaCO3, the DCM phase was concentrated to dryness. The solid residue was dissolved in 1 ml THF/MeOH/H2O (5:4:1). 0.06 ml of 1N NaOH were added and mixture was stirred at r.t for 1 h before worked up DCM//aq. NaCO3. DCM phase was concentrated and subjected to prep HPLC purification to give 3.7 mg of (2-chlorophenyl)-N-{2-[1-methyl-3-(trifluoromethyl)pyrazol-5-yl](1,3-thiazol-5-yl)}carboxamide (67) as yellow solid (yield: 31.9%; purity>90%). LC-MS: calcd. for C15H10ClF3N4OS: 387 (M+1).

Workup

  1. concentrationNaCO3, the DCM phase was concentrated to dryness
  2. dissolutionThe solid residue was dissolved in 1 ml THF/MeOH/H2O (5:4:1)
  3. addition0.06 ml of 1N NaOH were added
  4. stirringmixture was stirred at r.t for 1 h
  5. concentrationDCM phase was concentrated
  6. customHPLC purification

Sources & evidence

ORD record
ord-ed8b7be31ffe411685ef0186ebd80ddf
Source dataset
uspto-grants-2015_07
Patent number
US09079891B2

Reaction notes

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