1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(3-methyloxetan-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246586Notes

Reaction equation

HRID 246586 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21](O)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.[CH3:35][C:36]1([NH2:40])[CH2:39][O:38][CH2:37]1>CN(C=O)C.CN(C1C=CN=CC=1)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:40][C:36]5([CH3:35])[CH2:39][O:38][CH2:37]5)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 468357253-Amino-3-methyloxetaneHCID 712796392-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 712801632-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(3-methyloxetan-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 38.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (105 mg, 0.34 mmol) in 6 mL of DMF were added EDCI (128 mmol, 0.67 mmol), DMAP (82 mg, 0.67 mmol) and 3-methyloxetan-3-amine (44 mg, 0.50 mmol) in one portion at room temperature. Then the mixture was stirred for 16 hours. The solvent was evaporated at 70° C. under reduced pressure and the residue was triturated with water (10 mL), dichloromethane (10 mL), methanol (15 mL) then decanted and dried to give 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-(3-methyloxetan-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (50 mg, 38.9%) as a yellow solid. MS: (M+H)+=381; 1H NMR (300 MHz, DMSO): δ 12.90 (brs, 1H), 9.13 (s, 1H), 8.53-8.47 (m, 3H), 7.72 (d, 1H, J=7.8 Hz), 7.26-7.21 (m, 1H), 4.91 (d, 2H, J=6.0 Hz), 4.55 (d, 2H, J=6.3 Hz), 4.18 (s, 3H), 1.77 (s, 3H).

Workup

  1. customThe solvent was evaporated at 70° C. under reduced pressure
  2. customthe residue was triturated with water (10 mL), dichloromethane (10 mL), methanol (15 mL)
  3. customthen decanted
  4. customdried

Sources & evidence

ORD record
ord-f030c6b33bc5429da525ab436af3c8ee
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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