2-Chlorobenzoyl chloride → (2-chlorophenyl)-N-[5-(1-methylindol-2-yl)(1,3-thiazol-2-yl)]carboxamide

HRID 1524241Notes

Reaction equation

HRID 1524241 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11]1[S:15][C:14]([NH2:16])=[N:13][CH:12]=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:16][C:14]1[S:15][C:11]([C:3]2[N:2]([CH3:1])[C:10]3[C:5]([CH:4]=2)=[CH:6][CH:7]=[CH:8][CH:9]=3)=[CH:12][N:13]=1)=[O:21]

Participants

6

Reactant 3

HCID 691102-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 871477225-(1-Methylindol-2-yl)-1,3-thiazole-2-ylamine

Product 1

HCID 56848401(2-chlorophenyl)-N-[5-(1-methylindol-2-yl)(1,3-thiazol-2-yl)]carboxamideYield 97%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 5-(1-methylindol-2-yl)-1,3-thiazole-2-ylamine (53, 10 mg, 0.043 mmol) in 1 ml DCM were added 2-chlorobenzoyl chloride (11 μl, 2 eq), DIEA (37 μl, 3 eq) and DMAP (2 mg). After stirred at r.t for overnight, the reaction mixture was worked up with DCM/aq. NaCO3, the DCM phase was concentrated to dryness. The solid residue was dissolved in 2 ml THF/MeOH/H2O (5:4:1). 0.1 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 silica gel flash column to give 15.3 mg of (2-chlorophenyl)-N-[5-(1-methylindol-2-yl)(1,3-thiazol-2-yl)]carboxamide (54) as yellow solid (yield: 97%; purity>95%). LC-MS: calcd. for C18H14ClN3OS: 368 (M+1).

Workup

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

Sources & evidence

ORD record
ord-7b5820d061154c898c0f635c4f576e0e
Source dataset
uspto-grants-2015_07
Patent number
US09079891B2

Reaction notes

Loading…