racemic trans [3-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ester → racemic trans [3-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ester

HRID 1257684Notes

Reaction equation

HRID 1257684 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14]2[C:19]([N+:20]([O-])=O)=[CH:18][N:17]=[C:16]3[N:23]([S:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)(=[O:28])=[O:27])[CH:24]=[CH:25][C:15]=23)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]>C(O)(=O)C.[OH-].[Pd+2].[OH-]>[C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14]2[C:19]([NH2:20])=[CH:18][N:17]=[C:16]3[N:23]([S:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)(=[O:28])=[O:27])[CH:24]=[CH:25][C:15]=23)[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 131730635racemic trans [3-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ester

Product 1

HCID 131730636racemic trans [3-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl esterYield 52.1%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of racemic trans [3-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ester (23.7 g, 47.2 mmol) and palladium hydroxide (2.44 g, 20%) in acetic acid (285 mL) was stirred under an atmosphere of hydrogen at 50° C. for 3 hours and then room temperature for 18 hours. The mixture was filtered through Celite® and then concentrated in vacuo. The residue was dissolved in DCM, then washed (saturated sodium hydrogen carbonate solution (3×) and brine) and concentrated to dryness. Purification by column chromatography on silica gel (gradient: DCM to ethyl acetate) afforded 11.6 g (52%) of racemic trans [3-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-cyclopentyl]-carbamic acid tert-butyl ester as a purple solid. LCMS (Method B, ESI): RT=2.85 min, m+H=472.4; 1H NMR (400 MHz, DMSO) δ: 8.00 (d, 2H), 7.66 (t, 1H), 7.57 (t, 2H), 7.52 (s, 1H), 7.45 (d, 1H), 6.97 (d, 1H), 6.82 (d, 1H), 5.21 (d, 1H), 4.35 (m, 3H), 3.95 (m, 1H), 2.13-1.91 (m, 2H), 1.79 (m, 2H), 1.44 (m, 2H), 1.37 (s, 9H).

Workup

  1. waitroom temperature for 18 hours
  2. filtrationThe mixture was filtered through Celite®
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in DCM
  5. washwashed (saturated sodium hydrogen carbonate solution (3×) and brine)
  6. concentrationconcentrated to dryness
  7. customPurification by column chromatography on silica gel (gradient: DCM to ethyl acetate)

Sources & evidence

ORD record
ord-acf77ac3974c4b899087e8050235bc2a
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

Loading…