Water → HCID 71285814, compound

HRID 246214Notes

Reaction equation

HRID 246214 reaction equation
[OH:1][CH:2]([CH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1)[CH:3]([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][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])[CH3:4].C(Cl)Cl.C(N)CN.O>C(O)(C(F)(F)F)=O>[OH:1][CH:2]([CH:36]1[CH2:37][CH2:38][O:39][CH2:40][CH2:41]1)[CH:3]([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][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 6344DichloromethaneHCID 71286078HCID 71286078, compound

Product 1

HCID 71285814HCID 71285814, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

2-(6-Fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-hydroxy-1-methyl-2-(tetrahydro-pyran-4-yl)-ethyl]-amide, diastereomer B (70 mg, 0.120 mmol) was dissolved in a 4:6 solution of TFA:DCM (5.7 mL). After stirring at room temperature overnight, the volatiles were removed under reduced pressure. The crude material was then dissolved in dichloromethane and treated with ethylenediamine (722 mg, 12 mmol). After stirring at room temperature overnight, water was added and the resulting precipitate was collected by filtration to provide 30 mg (55%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-hydroxy-1-methyl-2-(tetrahydro-pyran-4-yl)-ethyl]-amide (diastereomer B) as an off-white solid. MS: (M+H)+=453. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.73 (br. s., 1H) 8.99-9.30 (m, 1H) 8.70 (dd, J=9.06, 5.29 Hz, 1H) 8.22-8.48 (m, 1H) 7.65 (dd, J=9.82, 1.89 Hz, 2H) 6.94-7.22 (m, 1H) 4.97 (d, J=6.80 Hz, 1H) 4.35 (m, 1H) 4.2 (s, 1H), 3.71 (m, 2H) 1.87 (d, J=13.60 Hz, 1H) 1.43-1.77 (m, 2H) 0.97-1.43 (m, 5H).

Workup

  1. customthe volatiles were removed under reduced pressure
  2. dissolutionThe crude material was then dissolved in dichloromethane
  3. stirringAfter stirring at room temperature overnight
  4. filtrationthe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-7fde1aad870b4a75ba489880574e3375
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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