Ethylenediamine → 2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-amide

HRID 245989

Reaction equation

HRID 245989 reaction equation
[CH3:1][C@@H:2]([NH:11][C:12]([C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([C:23]3[C:31]4[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=4)[N:25]([CH3:33])[N:24]=3)[N:21]=2)[N:16](COCC[Si](C)(C)C)[CH:15]=1)=[O:13])[CH2:3][C:4](=[O:10])[N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1.C(O)(C(F)(F)F)=O.C(N)CN>C(Cl)Cl>[CH3:1][C@@H:2]([NH:11][C:12]([C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([C:23]3[C:31]4[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=4)[N:25]([CH3:33])[N:24]=3)[N:21]=2)[NH:16][CH:15]=1)=[O:13])[CH2:3][C:4](=[O:10])[N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861682-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-amide

Product 1

HCID 712860562-(6-Chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-amideYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-amide (125 mg, 0.21 mmol) in CH2Cl2 (2 mL) was added TFA (0.5 mL, 6.49 mmol). The yellow reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was redissolved in CH2Cl2 (2 mL) and ethylenediamine (0.4 mL, 6.0 mmol) was added. The reaction mixture was stirred at room temperature for 1 h then quenched with water. The resultant precipitate was collected via filtration and washed with water and EtOAc. The solid was dissolved in 10% MeOH/CH2Cl2 and washed with water. The aqueous layer was back-extracted with CH2Cl2. The combined organics were dried over MgSO4 and concentrated to afford 64 mg (66%) of 2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-amide as an off-white solid. MS: (M+H)+=466; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.07 (s, 1H), 8.57 (d, J=8.7 Hz, 1H), 8.41 (s, 1H), 8.26 (d, J=7.9 Hz, 1H), 7.97 (d, J=1.1 Hz, 1H), 7.28 (dd, J=8.7, 1.5 Hz, 1H), 4.36-4.54 (m, 1H), 4.16 (s, 3H), 3.40 (t, J=6.6 Hz, 2H), 3.10-3.25 (m, 2H), 2.52-2.76 (m, 2H), 1.61-1.90 (m, 4H), 1.38 (d, J=6.8 Hz, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in CH2Cl2 (2 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. filtrationThe resultant precipitate was collected via filtration
  6. washwashed with water and EtOAc
  7. dissolutionThe solid was dissolved in 10% MeOH/CH2Cl2
  8. washwashed with water
  9. extractionThe aqueous layer was back-extracted with CH2Cl2
  10. dry with materialThe combined organics were dried over MgSO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-6b85256b0b11496094bfe3cf5efda18f
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

Loading…