Sodium Carbonate → (R)-tert-butyl 1-(4-(3-acetamido-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamate

HRID 79601Notes

Reaction equation

HRID 79601 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[NH:13][CH:14]=[C:15]([NH:16][C:17](=[O:19])[CH3:18])[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.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[C:17]([NH:16][C:15]1[C:8]2[C:9](=[N:10][CH:11]=[CH:12][C:7]=2[N:1]2[CH2:6][CH2:5][N:4]([C:29](=[O:30])[C@H:28]([NH:27][C:25](=[O:26])[O:24][C:20]([CH3:21])([CH3:22])[CH3:23])[CH2:32][C:33]3[CH:34]=[CH:35][C:36]([Cl:39])=[CH:37][CH:38]=3)[CH2:3][CH2:2]2)[NH:13][CH:14]=1)(=[O:19])[CH3:18]

Participants

8

Reactant 6

HCID 10340Sodium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 7018791N-Boc-4-chloro-D-phenylalanineHCID 68761313N-(4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetamide

Product 1

HCID 68760828(R)-tert-butyl 1-(4-(3-acetamido-1H-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamateYield 57.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Crude N-(4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetamide (0.050 g, 0.15 mmol, see Example 52), (R)-2-(tert-butoxycarbonylamino)-3-(4-chlorophenyl)propanoic acid (0.0496 g, 0.166 mmol), HOBT-H2O (0.0323 g, 0.211 mmol), and EDCI (0.0375 g, 0.196 mmol) were placed in DCM (5 mL). DIEA (d 0.742; 0.131 mL, 0.752 mmol) was then added, and the reaction was stirred for 5 hours. The reaction was then poured into saturated Na2CO3 and extracted into DCM. The organic fractions were combined, dried, filtered and concentrated to give a crude residue that was purified by column chromatography (500:13-500:18 DCM:MeOH) to give (R)-tert-butyl 1-(4-(3-acetamido-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-(4-chlorophenyl)-1-oxopropan-2-ylcarbamate (0.047 g, 57.7% yield).

Workup

  1. extractionextracted into DCM
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a crude residue that
  6. customwas purified by column chromatography (500:13-500:18 DCM:MeOH)

Sources & evidence

ORD record
ord-124a6b04e60946aab733ab684e880b75
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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