Ethylenediamine → HCID 71288253, compound

HRID 245985Notes

Reaction equation

HRID 245985 reaction equation
[CH3:1][S:2]([N:5]1[CH2:8][CH:7]([CH:9]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[N:16](COCC[Si](C)(C)C)[CH:15]=2)=[O:13])[CH3:10])[CH2:6]1)(=[O:4])=[O:3].C(O)(C(F)(F)F)=O.C(N)CN>C(Cl)Cl>[CH3:1][S:2]([N:5]1[CH2:6][CH:7]([CH:9]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[NH:16][CH:15]=2)=[O:13])[CH3:10])[CH2:8]1)(=[O:3])=[O:4]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712883082-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(1-methanesulfonyl-azetidin-3-yl)-ethyl]-amide

Product 1

HCID 71288253HCID 71288253, compoundYield 63%

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 [1-(1-methanesulfonyl-azetidin-3-yl)-ethyl]-amide (30 mg, 0.049 mmol) in CH2Cl2 (2 mL) was added TFA (0.3 mL, 3.89 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 (0.3 mL, 4.49 mmol) was added. The reaction mixture was stirred at room temperature for 1 h then quenched with water and extracted with MeOH/CH2Cl2 (1:9). The organic layer was washed with water and the aqueous was back-extracted with CH2Cl2. The combined organics were concentrated and the residue was triturated with MeOH/EtOAc/Et2O to afford 15 mg (63%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(1-methanesulfonyl-azetidin-3-yl)-ethyl]-amide as a pale yellow solid. MS (M+H)+=488; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.05 (br. s., 1H), 8.86 (s, 1H), 8.63 (s, 1H), 8.41 (d, J=8.7 Hz, 1H), 7.92 (s, 1H), 7.26 (d, J=8.7 Hz, 1H), 4.35-4.45 (m, 1H), 4.22-4.33 (m, 1H), 4.12 (s, 3H), 4.04-4.10 (m, 1H), 3.62-3.74 (m, 1H), 3.45-3.58 (m, 1H), 3.25 (s, 3H), 2.57-2.68 (m, 1H), 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. extractionextracted with MeOH/CH2Cl2 (1:9)
  6. washThe organic layer was washed with water
  7. extractionthe aqueous was back-extracted with CH2Cl2
  8. concentrationThe combined organics were concentrated
  9. customthe residue was triturated with MeOH/EtOAc/Et2O

Sources & evidence

ORD record
ord-5555deed5bf848818d2e51a68d58298f
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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