Isopropyl chloroformate → isopropyl (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate

HRID 1969575Notes

Reaction equation

HRID 1969575 reaction equation
[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([S:20]([C:23]5[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=5)(=[O:22])=[O:21])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH2:30])[CH2:4]1)[CH3:2].Cl[C:32]([O:34][CH:35]([CH3:37])[CH3:36])=[O:33]>C1COCC1>[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([S:20]([C:23]5[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=5)(=[O:22])=[O:21])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH:30][C:32](=[O:33])[O:34][CH:35]([CH3:37])[CH3:36])[CH2:4]1)[CH3:2]

Participants

4

Reactant 2

HCID 7917Isopropyl chloroformateHCID 58557840(1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine

Product 1

HCID 58557839isopropyl (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamateYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine (0.080 g, 0.19 mmol, Preparation #BB.1*) in THF (2 mL) was added TEA (0.079 mL, 0.565 mmol) and the solution was stirred at ambient temperature for about 10 min. To the reaction was added isopropyl chloroformate (1 M in toluene, 0.18 mL, 0.18 mmol) and the reaction mixture was stirred for about 1 h. The solvent was removed under reduced pressure and DCM (5 mL) and saturated aqueous NaHCO3 (2 mL) were added. The layers were separated and the organic layer was washed with brine (2 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give crude isopropyl (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylcarbamate (0.080 g, 60%) which was used without further purification: LC/MS (Table 1, Method b) Rt=2.33 min; MS m/z: 511 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred for about 1 h
  2. customThe solvent was removed under reduced pressure and DCM (5 mL) and saturated aqueous NaHCO3 (2 mL)
  3. additionwere added
  4. customThe layers were separated
  5. washthe organic layer was washed with brine (2 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6051aee3de754d49ac3b587d5eef2ad9
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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