Hydrochloric Acid → HCID 86677949, compound

HRID 246104

Reaction equation

HRID 246104 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29](O)=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.C([N:35]([CH2:39][CH3:40])[CH:36](C)C)(C)C.CN(C)CCCN=C=NCC.CC1CN1.Cl>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:17]=[C:16]4[C:18]([C:29]([N:35]5[CH2:36][CH:39]5[CH3:40])=[O:30])=[CH:19][N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:28])[CH3:27])[C:15]4=[N:14][CH:13]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 63772-MethylaziridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 86677949HCID 86677949, compoundYield 64.6%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (100 mg, 0.218 mmol) was suspended in dichloromethane (2.2 ml). 4-Dimethylaminopyridine (5.3 mg, 0.044 mmol), N,N-diisopropylethylamine (76 ul, 0.44 mmol) and then 1-(3-(dimethylamino)-propyl)-3-ethylcarbodiimide (84 mg, 0.44 mmol) were added. The solution was stirred for 5 min then cooled in an ice bath. 2-Methylaziridine (23 ul, 0.33 mmol) was added and the reaction was warmed to room temperature. Stirring was continued until judged to be complete by TLC then water, dilute HCl and ethyl acetate were added. The aqueous layer was extracted once more with ethyl acetate and the combined organic layers were washed with sodium bicarbonate solution and dried over sodium sulfate. After evaporation the residue was purified by silica gel chromatography (ethyl acetate/hexanes) to give 70 mg (64%) of [2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-(2-methyl-aziridin-1-yl)-methanone. 1H NMR (300 MHz, CDCl3) δ ppm 9.23 (s, 1H) 8.76 (d, J=8.7 Hz, 1H) 8.33 (s, 1H) 7.44 (s, 1H) 7.24 (d, J=8.7 Hz, 1H) 5.73 (s, 2H) 4.14 (s, 3H) 3.56-3.65 (m, 6H) 2.80-2.91 (m, 1H) 2.59 (d, J=6.0 Hz, 1H) 2.33 (d, J=3.8 Hz, 1H) 1.41 (d, J=5.3 Hz, 3H) 0.89-0.99 (m, 2H)-0.05 (s, 9H).

Workup

  1. temperaturethen cooled in an ice bath
  2. stirringStirring
  3. extractionThe aqueous layer was extracted once more with ethyl acetate
  4. washthe combined organic layers were washed with sodium bicarbonate solution
  5. dry with materialdried over sodium sulfate
  6. customAfter evaporation the residue
  7. customwas purified by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-fca5b22889e7498f9094416f8bddae61
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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