Phosphorus sulfide (P2S5) → 3-(5-chloromethyl-[1,3,4]thiadiazol-2-yl)-1-cyclohexylmethyl-7-methoxy-1H-indole

HRID 644078Notes

Reaction equation

HRID 644078 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][NH:6][C:7]([C:9]1[C:17]2[C:12](=[C:13]([O:18][CH3:19])[CH:14]=[CH:15][CH:16]=2)[N:11]([CH2:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[CH:10]=1)=O)=O.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:28]>O1CCCC1.ClCCl>[Cl:1][CH2:2][C:3]1[S:28][C:7]([C:9]2[C:17]3[C:12](=[C:13]([O:18][CH3:19])[CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:20][CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:10]=2)=[N:6][N:5]=1

Participants

5

Reactant 2

HCID 14817Phosphorus sulfide (P2S5)HCID 686955621-cyclohexylmethyl-7-methoxy-1H-indole-3-carboxylic acid N'-(2-chloroacetyl)hydrazide

Product 1

HCID 687020533-(5-chloromethyl-[1,3,4]thiadiazol-2-yl)-1-cyclohexylmethyl-7-methoxy-1H-indoleYield 352.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-cyclohexylmethyl-7-methoxy-1H-indole-3-carboxylic acid N′-(2-chloroacetyl)hydrazide (prepared as described in Example 37; 50 mg, 0.139 mmol) in tetrahydrofuran (0.5 ml) was added phosphorus pentasulfide (62 mg, 0.139 mmol) and the reaction mixture subjected to microwave irradiation at 150° C. for 5 minutes. The reaction was repeated twice on a 0.7 mmol scale. The combined reaction mixture was poured into a separating funnel and diluted with dichloromethane (60 ml). The organics were washed with 5% aqueous sodium carbonate (2×30 ml), brine (30 ml), dried over sodium sulfate and the solvent removed in vacuo. The resulting residue was purified by flash column chromatography to afford 3-(5-chloromethyl-[1,3,4]thiadiazol-2-yl)-1-cyclohexylmethyl-7-methoxy-1H-indole (186 mg, 0.49 mmol).

Workup

  1. customirradiation at 150° C. for 5 minutes
  2. customThe combined reaction mixture
  3. additionwas poured into a separating funnel
  4. washThe organics were washed with 5% aqueous sodium carbonate (2×30 ml), brine (30 ml)
  5. dry with materialdried over sodium sulfate
  6. customthe solvent removed in vacuo
  7. customThe resulting residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-1aa251b92b7549d1a73222a8ddd1feb3
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

Loading…