1-Chloroethyl chloroformate → HCID 69812443, compound

HRID 529115Notes

Reaction equation

HRID 529115 reaction equation
[N+:1]([C:4]1[CH:49]=[CH:48][C:7]([C:8]([O:10][C@H:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([N:20]4[C:40]5[C:35](=[C:36]([CH2:42][NH:43][CH:44]([CH3:46])[CH3:45])[C:37]([Cl:41])=[CH:38][CH:39]=5)[C:22]5([CH2:27][CH2:26][N:25](CC6C=CC=CC=6)[CH2:24][CH2:23]5)[CH2:21]4)[C:14]=3[C@H:13]([CH3:47])[CH2:12]2)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].C(Cl)(=O)OC(Cl)C>ClC(Cl)C>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:8]([O:10][C@H:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([N:20]4[C:40]5[C:35](=[C:36]([CH2:42][NH:43][CH:44]([CH3:46])[CH3:45])[C:37]([Cl:41])=[CH:38][CH:39]=5)[C:22]5([CH2:23][CH2:24][NH:25][CH2:26][CH2:27]5)[CH2:21]4)[C:14]=3[C@H:13]([CH3:47])[CH2:12]2)=[O:9])=[CH:48][CH:49]=1)([O-:3])=[O:2]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 68761835HCID 68761835, compound

Product 1

HCID 69812443HCID 69812443, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a stirred solution of (5R,7R)-4-(1′-benzyl-5-chloro-4-((isopropylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (17 mg, 0.025 mmol) in dichloroethane (0.5 mL) was added 1-chloroethyl carbonochloridate (8.1 μL, 0.075 mmol) at 0° C. The reaction mixture was heated at reflux overnight. After cooling, the solvents were evaporated in vacuo. The residue was dissolved in MeOH (1 mL) and heated at reflux for 1 hour. After cooling, the solvent was evaporated in vacuo. The residue was taken up in DCM, washed with saturated aqueous NaHCO3 solution and brine, dried, and concentrated. The residue was purified by column chromatography (4% 7N ammonia in MeOH/DCM) to give (5R,7R)-4-(5-chloro-4-((isopropylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (6 mg, 41%). LCMS (APCI+) m/z 591, 593 [M+H]+; Rt=2.78 min.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. temperatureAfter cooling
  4. customthe solvents were evaporated in vacuo
  5. dissolutionThe residue was dissolved in MeOH (1 mL)
  6. temperatureheated
  7. temperatureat reflux for 1 hour
  8. temperatureAfter cooling
  9. customthe solvent was evaporated in vacuo
  10. washwashed with saturated aqueous NaHCO3 solution and brine
  11. customdried
  12. concentrationconcentrated
  13. customThe residue was purified by column chromatography (4% 7N ammonia in MeOH/DCM)

Sources & evidence

ORD record
ord-a930a686ec274808bfa16e6d78cb0ecd
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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