Triethylamine → (5)-Tert-butyl 3-(4-(5-bromo-1h-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-3-oxopropyl(isopropyl)carbamate

HRID 79520Notes

Reaction equation

HRID 79520 reaction equation
N[C@H](CC1C=CC(Cl)=CC=1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[C:16]([Br:17])=[CH:15][N:14]=[C:13]3[NH:18][CH:19]=[CH:20][C:12]=23)[CH2:7][CH2:6]1)=[O:4].[C:29]([O:33][C:34]([N:36]([CH:49]([CH3:51])[CH3:50])[CH2:37][C@H:38]([C:42]1[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][CH:43]=1)C(O)=O)=[O:35])([CH3:32])([CH3:31])[CH3:30].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.C(N(CC)CC)C>C(Cl)Cl>[Br:17][C:16]1[C:11]([N:8]2[CH2:7][CH2:6][N:5]([C:3](=[O:4])[C@@H:38]([C:42]3[CH:43]=[CH:44][C:45]([Cl:48])=[CH:46][CH:47]=3)[CH2:37][N:36]([CH:49]([CH3:51])[CH3:50])[C:34](=[O:35])[O:33][C:29]([CH3:31])([CH3:32])[CH3:30])[CH2:10][CH2:9]2)=[C:12]2[CH:20]=[CH:19][NH:18][C:13]2=[N:14][CH:15]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 44123672(R)-2-amino-1-(4-(5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)propan-1-oneHCID 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acid

Product 1

HCID 68764847(5)-Tert-butyl 3-(4-(5-bromo-1h-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-3-oxopropyl(isopropyl)carbamateYield 60.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Bromo-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine dihydrochloride (0.100 g, 0.282 mmol, see Example 1), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.145 g, 0.424 mmol, see Example H), HOBT-H2O (0.0606 g, 0.395 mmol), EDCI (0.0704 g, 0.367 mmol), and triethylamine (0.0394 mL, 0.282 mmol) were stirred in DCM (5 mL) at room temperature for 5 hours. The reaction was then quenched with saturated Na2CO3 and extracted into DCM. The organics were dried, filtered, and concentrated to give the crude product. Purification (500:6 DCM:MeOH) gave (S)-tert-butyl 3-(4-(5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-3-oxopropyl(isopropyl)carbamate (0.103 g, 60.2% yield).

Workup

  1. customThe reaction was then quenched with saturated Na2CO3
  2. extractionextracted into DCM
  3. customThe organics were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customPurification (500:6 DCM:MeOH)

Sources & evidence

ORD record
ord-8a256ade946d4432a0c2d8bea1e9b971
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

Loading…