Sodium Carbonate → tert-butyl (2S)-2-(4-chlorophenyl)-3-(4-(5-(2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

HRID 79598Notes

Reaction equation

HRID 79598 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[C:10]2[CH:16]=[CH:15][NH:14][C:11]2=[N:12][CH:13]=1.[C:23]([O:27][C:28]([N:30]([CH:43]([CH3:45])[CH3:44])[CH2:31][C@H:32]([C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)[C:33](O)=[O:34])=[O:29])([CH3:26])([CH3:25])[CH3:24].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>[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([C@H:32]([C:33]([N:20]2[CH2:19][CH2:18][N:17]([C:9]3[C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])=[CH:13][N:12]=[C:11]4[NH:14][CH:15]=[CH:16][C:10]=34)[CH2:22][CH2:21]2)=[O:34])[CH2:31][N:30]([CH:43]([CH3:44])[CH3:45])[C:28](=[O:29])[O:27][C:23]([CH3:25])([CH3:24])[CH3:26])=[CH:37][CH:38]=1

Participants

8

Reactant 6

HCID 10340Sodium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 59564929(2S)-3-[tert-butoxycarbonyl(isopropyl)amino]-2-(4-chlorophenyl)propanoic acidHCID 687620895-(2-fluorophenyl)-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 86649340tert-butyl (2S)-2-(4-chlorophenyl)-3-(4-(5-(2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamateYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-(2-Fluorophenyl)-4-(piperazin-1-yl)-1H-pyrrolo[2,3-b]pyri dine (0.034 g, 0.0921 mmol), (S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (0.0330 g, 0.0967 mmol, see Example H), HOBT-H2O (0.0197 g, 0.129 mmol), and EDCI (0.0229 g, 0.120 mmol) were placed in DCM (5 mL) at room temperature. DIEA (d 0.742; 0.0802 mL, 0.460 mmol) was then added, and the reaction was stirred at room temperature 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 (500:10 DCM:MeOH) to give tert-butyl (2S)-2-(4-chlorophenyl)-3-(4-(5-(2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (0.040 g, 70.0% yield). MS APCI (+) m/z 520 detected.

Workup

  1. extractionextracted into DCM
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a crude residue that
  6. customwas purified by column chromatography (500:10 DCM:MeOH)

Sources & evidence

ORD record
ord-c1e75c9804c74771b8afa1de6688cd9c
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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