Water → (R)-tert-Butyl 1-(4-(5-bromo-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamate

HRID 79512Notes

Reaction equation

HRID 79512 reaction equation
Cl.Cl.[Br:3][C:4]1[C:5]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[C:6]2[CH:12]=[CH:11][NH:10][C:7]2=[N:8][CH:9]=1.[C:19]([O:23][C:24]([NH:26][C@H:27]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1)[C:28](O)=[O:29])=[O:25])([CH3:22])([CH3:21])[CH3:20].ON1C2C=CC=CC=2N=N1.O.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>C(Cl)Cl>[Br:3][C:4]1[C:5]([N:13]2[CH2:18][CH2:17][N:16]([C:28](=[O:29])[C@H:27]([NH:26][C:24](=[O:25])[O:23][C:19]([CH3:20])([CH3:21])[CH3:22])[CH2:31][C:32]3[CH:33]=[CH:34][C:35]([Cl:38])=[CH:36][CH:37]=3)[CH2:15][CH2:14]2)=[C:6]2[CH:12]=[CH:11][NH:10][C:7]2=[N:8][CH:9]=1

Participants

8

Reactant 6

HCID 962WaterHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 7018791N-Boc-4-chloro-D-phenylalanineHCID 687629915-Bromo-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine dihydrochloride

Product 1

HCID 68763825(R)-tert-Butyl 1-(4-(5-bromo-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamateYield 63.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Bromo-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine dihydrochloride (0.20 g, 0.56 mmol) and (R)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (0.677 g, 2.25 mmol) were placed in DCM (5 mL) at room temperature. 1-Hydroxybenzotriazole (“HOBT”)—H2O (0.121 g, 0.79 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (“EDCI”; 0.14 g, 0.73 mmol), and triethylamine (0.39 mL, 2.82 mmol) were then added, and the reaction was stirred at room temperature for 18 hours. The reaction was then quenched with saturated Na2CO3 and extracted with DCM. The combined organic fractions were dried, filtered, and concentrated to give a crude residue. The crude residue was purified by column chromatography (500:7 DCM:MeOH) to give (R)-tert-butyl 1-(4-(5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamate (0.20 g, 62.9% yield).

Workup

  1. customThe reaction was then quenched with saturated Na2CO3
  2. extractionextracted with DCM
  3. customThe combined organic fractions were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a crude residue
  7. customThe crude residue was purified by column chromatography (500:7 DCM:MeOH)

Sources & evidence

ORD record
ord-6a5dc7fd30484519a51273a6e0fc1bf0
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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