Phosphorus sulfide (P2S5) → 6-chloro-4'-[5-chloro-2-(2-methanesulfonylamino-1,1-diethyl-2-oxo-ethoxy)-phenyl]-2'-(5-chloro-2-methyl-phenyl)-6'-thioxo spiro[3H-indole-3,3'-piperidine]-2(1H)-one

HRID 658925Notes

Reaction equation

HRID 658925 reaction equation
C([N:4]1[C:46]2[C:41](=[CH:42][CH:43]=[C:44]([Cl:47])[CH:45]=2)[C:6]2([CH:11]([C:12]3[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=3[O:19][C:20]([CH2:30][CH3:31])([CH2:28][CH3:29])[C:21]([NH:23][S:24]([CH3:27])(=[O:26])=[O:25])=[O:22])[CH2:10][C:9](=O)[NH:8][CH:7]2[C:33]2[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=2[CH3:40])[C:5]1=[O:48])(=O)C.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:50]>C1COCC1.C1(C)C=CC=CC=1>[Cl:47][C:44]1[CH:45]=[C:46]2[NH:4][C:5](=[O:48])[C:6]3([CH:11]([C:12]4[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=4[O:19][C:20]([CH2:30][CH3:31])([CH2:28][CH3:29])[C:21]([NH:23][S:24]([CH3:27])(=[O:25])=[O:26])=[O:22])[CH2:10][C:9](=[S:50])[NH:8][CH:7]3[C:33]3[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:41]2=[CH:42][CH:43]=1

Participants

5

Reactant 2

HCID 14817Phosphorus sulfide (P2S5)HCID 667698831-acetyl-6-chloro-4'-[5-chloro-2-(1-ethyl-1-methanesufonylaminocarbonyl-propoxy)-phenyl]-2'-(5-chloro-2-methyl-phenyl)-spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 752934046-chloro-4'-[5-chloro-2-(2-methanesulfonylamino-1,1-diethyl-2-oxo-ethoxy)-phenyl]-2'-(5-chloro-2-methyl-phenyl)-6'-thioxo spiro[3H-indole-3,3'-piperidine]-2(1H)-oneYield 88.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of chiral (2′S, 3S, 4′R)-1-acetyl-6-chloro-2′-(5-chloro-2-methyl-phenyl)-4′-[5-chloro-2-(2-methanesulfonylamino-1,1-diethyl-2-oxo-ethoxy)-phenyl]-spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (30 mg, 0.04 mmol) and P2S5 (26 mg, 0.12 mmol) in THF (2 mL) was stirred at room temperature overnight, then diluted with toluene (10 mL). The resultant mixture was concentrated and washed with DCM for two times. The DCM solution was collected and purified by flash column chromtography. The product was then stirred with K2CO3 (20 mg) in MeOH for 15 min, and then partitioned between ethyl acetate and diluted HCl solution. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated to give the title product as white solid (25 mg).

Workup

  1. concentrationThe resultant mixture was concentrated
  2. washwashed with DCM for two times
  3. customThe DCM solution was collected
  4. custompurified by flash column chromtography
  5. stirringThe product was then stirred with K2CO3 (20 mg) in MeOH for 15 min
  6. custompartitioned between ethyl acetate and diluted HCl solution
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-a71fd9ad863f4ad7beb91dbc3c70534c
Source dataset
uspto-grants-2011_12
Patent number
US08076482B2

Reaction notes

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