(r)-Tert-butyl 1-(4-(5-carbamoyl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamate → (R)-4-(4-(2-amino-3-(4-chlorophenyl)propanoyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile

HRID 79519Notes

Reaction equation

HRID 79519 reaction equation
[C:1]([C:4]1[C:5]([N:13]2[CH2:18][CH2:17][N:16]([C:19](=[O:37])[C@H:20]([NH:29]C(=O)OC(C)(C)C)[CH2:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:15][CH2:14]2)=[C:6]2[CH:12]=[CH:11][NH:10][C:7]2=[N:8][CH:9]=1)(=O)[NH2:2]>O=P(Cl)(Cl)Cl>[NH2:29][C@H:20]([CH2:21][C:22]1[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=1)[C:19]([N:16]1[CH2:17][CH2:18][N:13]([C:5]2[C:4]([C:1]#[N:2])=[CH:9][N:8]=[C:7]3[NH:10][CH:11]=[CH:12][C:6]=23)[CH2:14][CH2:15]1)=[O:37]

Participants

3

Reactant 1

HCID 68761929(r)-Tert-butyl 1-(4-(5-carbamoyl-1h-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamate

Product 1

HCID 44198751(R)-4-(4-(2-amino-3-(4-chlorophenyl)propanoyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrileYield 7.4%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
70 °C

Procedure

(R)-tert-Butyl 1-(4-(5-carbamoyl-1H-pyrrolo[2,3-b]pyri din-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamate (0.035 g, 0.066 mmol) was placed in POCl3 (2 mL) and heated to 70° C. for 2 hours. The reaction was then concentrated, diluted with DCM, and washed with saturated NaHCO3. The organic fraction was dried, filtered and concentrated to give a crude residue. The residue was purified (SP4, 12+M, water/CAN 95/5→60/40, 20CV) to give (R)-4-(4-(2-amino-3-(4-chlorophenyl)propanoyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (0.002 g, 7.4% yield). MS ESI (+) m/z 409 detected.

Workup

  1. concentrationThe reaction was then concentrated
  2. additiondiluted with DCM
  3. washwashed with saturated NaHCO3
  4. customThe organic fraction was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude residue
  8. customThe residue was purified (SP4, 12+M, water/CAN 95/5→60/40, 20CV)

Sources & evidence

ORD record
ord-674da9d08c5d42b79b70932db553a418
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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