1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl 2-(4-(5-bromo-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethylcarbamate

HRID 79615Notes

Reaction equation

HRID 79615 reaction equation
[Br:1][C:2]1[C:3]([N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[C:4]2[C:10]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[C:26]([O:30][C:31]([NH:33][CH2:34][C:35](O)=[O:36])=[O:32])([CH3:29])([CH3:28])[CH3:27].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C(Cl)Cl.CN1C(=O)CCC1>[Br:1][C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23]([C:35](=[O:36])[CH2:34][NH:33][C:31](=[O:32])[O:30][C:26]([CH3:27])([CH3:28])[CH3:29])[CH2:22][CH2:21]2)=[C:4]2[C:10]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 68764294HCID 68764294, compound

Product 1

HCID 68781630tert-butyl 2-(4-(5-bromo-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethylcarbamateYield 40.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

The above NMP solution of N-(5-bromo-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.200 g, 0.498 mmol), 2-(tert-butoxycarbonylamino)acetic acid (0.114 g, 0.648 mmol), HOBT-H2O (0.107 g, 0.698 mmol), and EDCI (0.124 g, 0.648 mmol) were placed in DCM (3 mL). DIEA (d 0.742; 0.434 mL, 2.49 mmol) was then added, and the reaction was stirred at room temperature for 4 hours. The reaction was then quenched with saturated Na2CO3 and extracted into DCM. The organic fractions were combined, dried, filtered, and concentrated to give the crude residue. Purification by column chromatography (500:15 to 500:25 DCM:MeOH) gave tert-butyl 2-(4-(5-bromo-3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-oxoethylcarbamate (0.112 g, 40.2% yield).

Workup

  1. customThe reaction was then quenched with saturated Na2CO3
  2. extractionextracted into DCM
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude residue
  7. customPurification by column chromatography (500:15 to 500:25 DCM:MeOH)

Sources & evidence

ORD record
ord-fdc2f122257046e6be8338696e509ab1
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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