Cesium carbonate → HCID 71279969, compound

HRID 246402Notes

Reaction equation

HRID 246402 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[NH:19][N:18]=3)[N:15]=2)[N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].Cl[CH2:40][CH2:41][CH2:42][NH+:43]([CH3:45])[CH3:44].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.ClCCl>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:28])[F:29])[CH:24]=4)[N:19]([CH2:40][CH2:41][CH2:42][N:43]([CH3:45])[CH3:44])[N:18]=3)[N:15]=2)[N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 111056195407-04-5HCID 712795662-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

Product 1

HCID 71279969HCID 71279969, compoundYield 77.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

In a 2-(5 mL Biotage microwave vial were mixed N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (109 mg, 205 μmol), 3-chloro-N,N-dimethylpropan-1-aminium chloride (97.4 mg, 616 μmol, Eq: 3.0) and Cs2CO3 (402 mg, 1.23 mmol, Eq: 6.00) in DMF (2 mL). The mixture was stirred ˜10 min at 25° C. then heated to 100° C. in the Biotage microwave reactor for 30 min, diluted with 10 mL of dichloromethane and filtered through a celite pad, filtrate concentrated under high vacuum at 65° C. and residue dissolved in dichloromethane and purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (97 mg, 158 μmol, 76.7%) as a light brown solid. MS (M+H)+=616 (>90% purity); 1H NMR (CDCl3) δ: 9.24 (s, 1H), 8.36 (s, 1H), 8.32 (d, J=2.3 Hz, 1H), 8.06 (s, 1H), 7.60 (d, J=8.7 Hz, 1H), 7.35 (dd, J=9.1, 2.3 Hz, 1H), 6.55 (t, J=74.8 Hz, 1H), 5.75 (s, 2H), 4.60 (t, J=6.6 Hz, 2H), 3.53-3.74 (m, 2H), 2.33-2.42 (m, 2H), 2.29 (s, 6H), 2.14-2.27 (m, 2H), 1.65 (s, 9H), 0.90-1.07 (m, 2H), 0.00 (s, 9H).

Workup

  1. temperaturethen heated to 100° C. in the Biotage microwave reactor for 30 min
  2. filtrationfiltered through a celite pad, filtrate
  3. concentrationconcentrated under high vacuum at 65° C.
  4. dissolutionresidue dissolved in dichloromethane
  5. custompurified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
  6. washeluting with 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane

Sources & evidence

ORD record
ord-287238e6fe1d40c98f907126fe7545b9
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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