Thiazole → HCID 118323986, compound

HRID 1778274Notes

Reaction equation

HRID 1778274 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[Cl:11][C:12]1[CH:40]=[CH:39][C:15]([C:16]([C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[N:24]([CH3:28])[C:23](=[O:29])[CH:22]=[C:21]3[CH2:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[CH:33]=2)=[O:17])=[CH:14][CH:13]=1>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[Cl:38][C:34]1[CH:33]=[C:32]([CH:37]=[CH:36][CH:35]=1)[CH2:31][CH2:30][C:21]1[C:20]2[C:25](=[CH:26][CH:27]=[C:18]([C:16]([C:15]3[CH:39]=[CH:40][C:12]([Cl:11])=[CH:13][CH:14]=3)([OH:17])[C:2]3[S:1][CH:5]=[CH:4][N:3]=3)[CH:19]=2)[N:24]([CH3:28])[C:23](=[O:29])[CH:22]=1

Participants

6

Reactant 3

HCID 9256ThiazoleHCID 21909064HCID 21909064, compound2×HCID 178418339Butyllithium

Product 1

HCID 118323986HCID 118323986, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

To a solution of thiazole (195 mg, 2.292 mmol, 2.00 equip) in THF (10 mL) at −78° C. was added n-butyllithium (1.6 M in hexanes, 1.447 mL, 2.315 mmol, 2.02 equip) dropwise. After 30 minutes, a solution of 6-(4-chlorobenzoyl)-4-(3-chlorophenethyl)-1-methylquinolin-2(1H)-one (500 mg, 1.146 mmol, 1 equip, prepared as described in ANGIBAUD, P. R., et al., PCT Publication WO2002/051835 A1, published 4 Jul. 2002) in HMPA (8 mL) was added dropwise and the reaction mixture was warmed to room temperature. The reaction was stirred overnight, then quenched with water and the resulting mixture extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried (Na2SO4), and concentrated. The residue was purified by MPLC using methanol-dichloromethane as the eluent to yield 4-(3-chlorophenethyl)-6-((4-chlorophenyl)(hydroxy)(thiazol-2-yl)methyl)-1-methylquinolin-2(1H)-one as a tan solid.

Workup

  1. customquenched with water
  2. extractionthe resulting mixture extracted with dichloromethane (3×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by MPLC

Sources & evidence

ORD record
ord-8079779ebfe746c4b5d38425f40228a2
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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