Water → 2-(5-difluoromethoxy-1-pyrrolidin-3-ylmethyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246309Notes

Reaction equation

HRID 246309 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([CH2:13][N:14]2[C:22]3[C:17](=[CH:18][C:19]([O:23][CH:24]([F:26])[F:25])=[CH:20][CH:21]=3)[C:16]([C:27]3[N:28]=[C:29]4[C:35]([C:36](=[O:42])[NH:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][N:33](COCC[Si](C)(C)C)[C:30]4=[N:31][CH:32]=3)=[N:15]2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[C:38]([NH:37][C:36]([C:35]1[C:29]2[C:30](=[N:31][CH:32]=[C:27]([C:16]3[C:17]4[C:22](=[CH:21][CH:20]=[C:19]([O:23][CH:24]([F:25])[F:26])[CH:18]=4)[N:14]([CH2:13][CH:10]4[CH2:11][CH2:12][NH:8][CH2:9]4)[N:15]=3)[N:28]=2)[NH:33][CH:34]=1)=[O:42])([CH3:41])([CH3:39])[CH3:40]

Participants

7

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712801373-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-ylmethyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 712799282-(5-difluoromethoxy-1-pyrrolidin-3-ylmethyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 36.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a round-bottomed flask, 3-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-ylmethyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (134 mg, 0.188 mmol) was dissolved in dichloromethane (1 ml) and trifluoroacetic acid (0.58 ml, 7.53 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (1 ml) and ethylenediamine (0.76 ml, 11.3 mmol) was added. The light yellow solution was stirred at room temperature for 45 min then water and ethyl acetate were added. The resulting suspension was filtered and washed with hot water and ethyl acetate then dried under high vacuum to provide 33 mg (35%) of 2-(5-difluoromethoxy-1-pyrrolidin-3-ylmethyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow powder. MS: (M+H)+=484; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.06 (s, 1H), 8.38 (s, 1H), 8.21 (s, 1H), 7.94 (d, J=9.1 Hz, 1H), 7.88 (s, 1H), 7.40 (d, J=9.1 Hz, 1H), 7.20 (t, J=74.8 Hz, 1H), 4.50 (d, J=6.8 Hz, 2H), 2.58-2.97 (m, 6H), 1.69-1.84 (m, 1H), 1.51 (s, 9H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (1 ml)
  3. stirringThe light yellow solution was stirred at room temperature for 45 min
  4. filtrationThe resulting suspension was filtered
  5. washwashed with hot water and ethyl acetate
  6. customthen dried under high vacuum

Sources & evidence

ORD record
ord-9665667d24d5426a93bae24270eaf6db
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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