Triethylamine → (R)-Methyl 4-(4-(2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoyl)piperazin-1-yl)-1H-pyrrolo [2,3-b]pyridine-5-carboxylate

HRID 79516Notes

Reaction equation

HRID 79516 reaction equation
[N:1]1([C:7]2[C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][N:10]=[C:9]3[NH:17][CH:18]=[CH:19][C:8]=23)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:20]([O:24][C:25]([NH:27][C@H:28]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=1)[C:29](O)=[O:30])=[O:26])([CH3:23])([CH3:22])[CH3:21].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.C(N(CC)CC)C>C(Cl)Cl>[C:20]([O:24][C:25]([NH:27][C@H:28]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=1)[C:29]([N:4]1[CH2:3][CH2:2][N:1]([C:7]2[C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][N:10]=[C:9]3[NH:17][CH:18]=[CH:19][C:8]=23)[CH2:6][CH2:5]1)=[O:30])=[O:26])([CH3:23])([CH3:21])[CH3:22]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 7018791N-Boc-4-chloro-D-phenylalanineHCID 68762011methyl 4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

Product 1

HCID 68765221(R)-Methyl 4-(4-(2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoyl)piperazin-1-yl)-1H-pyrrolo [2,3-b]pyridine-5-carboxylateYield 29.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (0.23 g, 0.69 mmol) and (R)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (0.227 g, 0.759 mmol) were placed in DCM (5 mL) at room temperature. HOBT-H2O (0.147 g, 0.966 mmol), EDCI (0.172 g, 0.897 mmol) and triethylamine (0.48 mL, 3.45 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 residue was purified by column chromatography (500:7 DCM:MeOH) to give (R)-methyl 4-(4-(2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (0.11 g, 29.4% 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 residue was purified by column chromatography (500:7 DCM:MeOH)

Sources & evidence

ORD record
ord-0f0cfbb3cb3e48468f0960affb63a006
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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