1-Chloroethyl chloroformate → HCID 71240477, compound

HRID 80809Notes

Reaction equation

HRID 80809 reaction equation
C([N:8]1[CH2:56][CH2:55][C:11]2[N:12]=[C:13]([C:35]3[CH:43]=[CH:42][CH:41]=[C:40]4[C:36]=3[C:37]([CH3:54])=[CH:38][N:39]4[S:44]([C:47]3[CH:53]=[CH:52][C:50]([CH3:51])=[CH:49][CH:48]=3)(=[O:46])=[O:45])[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][N:19]([S:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[N+:31]([O-:33])=[O:32])(=[O:24])=[O:23])[C@H:18]([CH3:34])[CH2:17]3)[C:10]=2[CH2:9]1)C1C=CC=CC=1.C(Cl)(=O)OC(Cl)C>CC#N>[CH3:54][C:37]1[C:36]2[C:40](=[CH:41][CH:42]=[CH:43][C:35]=2[C:13]2[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][N:19]([S:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[N+:31]([O-:33])=[O:32])(=[O:24])=[O:23])[C@H:18]([CH3:34])[CH2:17]3)[C:10]3[CH2:9][NH:8][CH2:56][CH2:55][C:11]=3[N:12]=2)[N:39]([S:44]([C:47]2[CH:48]=[CH:49][C:50]([CH3:51])=[CH:52][CH:53]=2)(=[O:45])=[O:46])[CH:38]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 71240482(R)-6-benzyl-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 71240477HCID 71240477, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (R)-6-benzyl-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (1.17 g, 1.47 mmol) in MeCN (15 mL) was added 1-chloroethyl carbonochloridate (0.18 mL, 1.62 mmol), and the mixture was stirred for 15 minutes at which time the mixture was concentrated in vacuo. The resulting residue was dissolved in a 2:1 mixture of dichloromethane:methanol (15 mL) and heated at 40° C. for 1 hour and then placed at room temperature for ca. 15 h. The mixture was then diluted with dichloromethane and saturated aqueous sodium bicarbonate. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic layers were combined dried over Na2SO4, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (3-12% MeOH/DCM) to provide (R)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. MS (ESI+) m/z 702.3 (M+H)+.

Workup

  1. concentrationwas concentrated in vacuo
  2. dissolutionThe resulting residue was dissolved in a 2:1 mixture of dichloromethane
  3. waitplaced at room temperature for ca. 15 h
  4. additionThe mixture was then diluted with dichloromethane and saturated aqueous sodium bicarbonate
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted two additional times with dichloromethane
  7. dry with materialThe organic layers were combined dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel flash chromatography (3-12% MeOH/DCM)

Sources & evidence

ORD record
ord-aebcebbfc4874f74b5263cbbe8faa7da
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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