1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl 3-methyl-3-(2-(6-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)pyrrolidine-1-carboxylate

HRID 246681Notes

Reaction equation

HRID 246681 reaction equation
[CH3:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([C:20]([OH:22])=O)=[CH:18][NH:17][C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.[NH2:43][C:44]1([CH3:56])[CH2:48][CH2:47][N:46]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45]1>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[CH3:56][C:44]1([NH:43][C:20]([C:19]2[C:13]3[C:14](=[N:15][CH:16]=[C:11]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([CH3:1])=[CH:3][CH:4]=5)[NH:8][N:7]=4)[N:12]=3)[NH:17][CH:18]=2)=[O:22])[CH2:48][CH2:47][N:46]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45]1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 57415917tert-Butyl 3-amino-3-methylpyrrolidine-1-carboxylateHCID 712798942-(6-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71279771tert-butyl 3-methyl-3-(2-(6-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)pyrrolidine-1-carboxylateYield 47%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-(6-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.34 mmol), EDCI (123 mg, 0.64 mmol), DMAP (110 mg, 0.90 mmol) and DIEA (131 mg, 1.02 mmol) in 6 mL of DMF was added tert-butyl 3-amino-3-methylpyrrolidine-1-carboxylate (100 mg, 0.54 mmol) in one portion at room temperature, then the mixture was stirred for 16 hours. The reaction mixture was poured into 40 mL of water, extracted with ethyl acetate (150 mL). The organic phase was evaporated at 40° C. under reduced pressure and the residue was triturated with petroleum ether then decanted and dried to give crude tert-butyl 3-methyl-3-(2-(6-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamido)pyrrolidine-1-carboxylate (76 mg, 47.0%) as a yellow solid. MS: (M+H)+=476.2.

Workup

  1. extractionextracted with ethyl acetate (150 mL)
  2. customThe organic phase was evaporated at 40° C. under reduced pressure
  3. customthe residue was triturated with petroleum ether
  4. customthen decanted
  5. customdried

Sources & evidence

ORD record
ord-8987d4a3451940009d2b085003e4de98
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…