Sodium Carbonate → tert-Butyl (1S,2R)-2-(4-(benzofuran-3-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

HRID 516036Notes

Reaction equation

HRID 516036 reaction equation
Cl[C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]2[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[O:45]1[C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=2[C:47](B2OC(C)(C)C(C)(C)O2)=[CH:46]1>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[O:45]1[C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=2[C:47]([C:2]2[C:7]3[C:8](=[O:22])[N:9]([CH2:11][C:12]4[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=4[O:20][CH3:21])[CH2:10][C:6]=3[C:5]([F:23])=[C:4]([NH:24][C@@H:25]3[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]3[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:3]=2)=[CH:46]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 438110312-(1-Benzofuran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86654712tert-Butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

Product 1

HCID 86654720tert-Butyl (1S,2R)-2-(4-(benzofuran-3-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamateYield 48.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of tert-butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (65 mg, 0.118 mmol), aqueous sodium carbonate (2 N, 0.237 mL, 0.474 mmol), 2-(benzofuran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (43 mg, 0.178 mmol) and bis(triphenylphosphine)palladium chloride (17 mg, 0.024 mmol) in DME (2 mL) was placed in a vial. The vial was purged with nitrogen, sealed, and the reaction mixture heated at 120° C. for 1 h. The mixture was filtered through a pad of Celite, which was rinsed with MeOH. The solvent was removed in vacuo and the residue diluted with MeOH, passed through a microfiltration frit, and purified via preparative HPLC. The fractions were collected and concentrated in vacuo to give the title compound as a tan oil (36.3 mg, 48%). [M+H] calc'd for C35H39FN4O6, 632; found, 632.

Workup

  1. customThe vial was purged with nitrogen
  2. customsealed
  3. filtrationThe mixture was filtered through a pad of Celite, which
  4. washwas rinsed with MeOH
  5. customThe solvent was removed in vacuo
  6. additionthe residue diluted with MeOH
  7. custompurified via preparative HPLC
  8. customThe fractions were collected
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a30b6851c17a47d285e5672a75b70b7c
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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