Ethylenediamine → 2-(6-Fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amide

HRID 246017Notes

Reaction equation

HRID 246017 reaction equation
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([C@H: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]([F: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])[CH:4]=1.C(O)(C(F)(F)F)=O.C(N)CN>C(Cl)Cl>[F:43][C:2]([F:1])([F:42])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([C@H: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]([F: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])[CH:4]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712882332-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amide

Product 1

HCID 712861592-(6-Fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amideYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amide (122 mg, 0.20 mmol) in CH2Cl2 (3 mL) was added TFA (1 mL, 13.0 mmol). The bright yellow-orange reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was redissolved in CH2Cl2 (3 mL) and ethylene diamine (0.5 mL, 7.50 mmol) was added. The reaction mixture was stirred for 1 h then quenched with water and extracted with 5% MeOH/CH2Cl2 (2×). The combined organics were concentrated and triturated with MeOH/CH2Cl2 to isolate 65 mg (68%) of 2-(6-Fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amide as an off-white solid. MS: (M+Na)+=506; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.79 (br. s., 1H), 9.12 (s, 1H), 8.86 (d, J=7.9 Hz, 1H), 8.71-8.81 (m, 2H), 8.43 (s, 1H), 7.91 (s, 1H), 7.60-7.73 (m, 2H), 7.03 (td, J=9.2, 2.1 Hz, 1H), 5.55 (quin, J=7.3 Hz, 1H), 4.15 (s, 3H), 1.64 (d, J=6.8 Hz, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in CH2Cl2 (3 mL)
  3. stirringThe reaction mixture was stirred for 1 h
  4. customthen quenched with water
  5. extractionextracted with 5% MeOH/CH2Cl2 (2×)
  6. concentrationThe combined organics were concentrated
  7. customtriturated with MeOH/CH2Cl2

Sources & evidence

ORD record
ord-0555ada034184776b08de57eb3b48a6b
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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