Methanol → N-(3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentyl)cyclopropanesulfonamide

HRID 1969837Notes

Reaction equation

HRID 1969837 reaction equation
[CH3:1][CH:2]1[CH:6]([C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:13]=4[N:14]=[CH:15][C:10]3=[N:9][CH:8]=2)[CH2:5][CH:4]([NH2:27])[CH2:3]1.CCN(C(C)C)C(C)C.[CH:37]1([S:40](Cl)(=[O:42])=[O:41])[CH2:39][CH2:38]1.CO>C(Cl)Cl>[CH3:1][CH:2]1[CH:6]([C:7]2[N:11]3[C:12]4[CH:18]=[CH:17][N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:13]=4[N:14]=[CH:15][C:10]3=[N:9][CH:8]=2)[CH2:5][CH:4]([NH:27][S:40]([CH:37]2[CH2:39][CH2:38]2)(=[O:42])=[O:41])[CH2:3]1

Participants

6

Reactant 4

HCID 887MethanolHCID 81531Diisopropylethylamine2×HCID 2760919Cyclopropanesulfonyl chloride2×HCID 585575733-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentanamine

Product 1

HCID 58557168N-(3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentyl)cyclopropanesulfonamideYield 52.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentanamine (0.27 g, 0.7 mmol) and DIEA (0.18 mL, 1.05 mmol) in DCM (5 mL) was added cyclopropanesulfonyl chloride (0.098 g, 0.7 mmol) drop-wise. The resulting mixture was stirred at ambient temperature for about 1 h. Another 0.18 mL of DIEA and 0.098 g of cyclopropanesulfonyl chloride were added and the reaction was continued for about 3 h. The solvent was removed and the residue was partitioned between saturated aqueous ammonium chloride and EtOAc (20 mL each). The organic layer was washed with brine (10 mL), dried over anhydrous MgSO4, filtered and concd. The residue was purified by silica gel chromatography (100% DCM for 5 min, then to 6% MeOH in DCM over next 30 min) to yield N-(3-methyl-4-(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)cyclopentyl)cyclopropanesulfonamide (0.18 g, 52% yield) as an off-white solid. LC/MS (Table 1, Method a) Rt=2.45 min; MS m/z 490 (M+H)+.

Workup

  1. waitthe reaction was continued for about 3 h
  2. customThe solvent was removed
  3. customthe residue was partitioned between saturated aqueous ammonium chloride and EtOAc (20 mL each)
  4. washThe organic layer was washed with brine (10 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customThe residue was purified by silica gel chromatography (100% DCM for 5 min

Sources & evidence

ORD record
ord-0235329ce7b74294909f0feb55755828
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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