Nitrogen → tert-butyl3-((4-(ethylsulfonyl)benzyl)carbamoyl)-7-(tetrahydrofuran-3-yl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate

HRID 1777838Notes

Reaction equation

HRID 1777838 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[N:11][CH:12]=[C:13](Cl)[CH:14]=2)[CH:9]1[CH:18]1[CH2:22][CH2:21][O:20][CH2:19]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:23]([S:25]([C:28]1[CH:33]=[CH:32][C:31]([CH2:34][NH2:35])=[CH:30][CH:29]=1)(=[O:27])=[O:26])[CH3:24].N12CCCN=C1CCCCC2.N#N.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[O:67]1CCOC[CH2:68]1>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo]>[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:68](=[O:67])[NH:35][CH2:34][C:31]3[CH:32]=[CH:33][C:28]([S:25]([CH2:23][CH3:24])(=[O:27])=[O:26])=[CH:29][CH:30]=3)[CH:14]=2)[CH:9]1[CH:18]1[CH2:22][CH2:21][O:20][CH2:19]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 6

HCID 947NitrogenHCID 312751,4-DioxaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 179666261-[4-(Ethylsulfonyl)phenyl]methanamineHCID 118274928tert-butyl 3-chloro-7-(tetrahydrofuran-3-yl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate

Product 1

HCID 118274956tert-butyl3-((4-(ethylsulfonyl)benzyl)carbamoyl)-7-(tetrahydrofuran-3-yl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylateYield 26%

Reagents, catalysts & solvents 1

HCID 98885Molybdenum carbonyl (Mo(CO)6)Catalyst

Conditions

Temperature
160 °C

Procedure

To a solution of tert-butyl3-chloro-7-(tetrahydrofuran-3-yl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate (60 mg, 0.19 mmol) in a MW vial in anhydrous dioxane (0.5 mL) was added molybdenum hexacarbonyl (6 mg, 0.02 mmol), (4-(ethylsulfonyl)phenyl)methanamine (56 mg, 0.28 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (90 mg, 0.57 mmol). The mixture was degassed with N2 for 15 min, at which point tri-tert-butylphosphonium tetrafluoroborate (58 mg, 0.19 mmol) and trans-bis(acetate)bis[o-(di-o-tolylphosphino)benzyl]dipalladium (II) (10 mg, 0.01 mmol) were added. The vial was sealed and heated in the MW at 160° C. for 20 min. The reaction mixture was filtered, then the filtrate was concentrated under reduced pressure and purified by preparative TLC (eluting with 12% EtOAc in petroleum ether) to afford tert-butyl3-((4-(ethylsulfonyl)benzyl)carbamoyl)-7-(tetrahydrofuran-3-yl)-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxylate (25 mg, 26%) as a colorless oil. LCMS: tR=0.761 min in 5-95AB—1.5 min chromatography (MK RP18e 25-2 mm), MS (ESI) m/z 516.2 [M+H]+. 1H NMR (CD3OD, 400 MHz): δ 8.96 (s, 1H), 8.20 (d, J=10.0 Hz, 1H), 8.15-8.00 (m, 1H), 7.91 (d, J=8.4 Hz, 2H), 7.65 (d, J=8.0 Hz, 2H), 5.19 (s, 1H), 5.00-4.90 (m, 2H), 4.75-4.60 (m, 3H), 4.00-3.65 (m, 5H), 3.25 (q, J=7.2 Hz, 2H), 3.05-2.95 (m, 1H), 2.15-1.75 (m, 2H), 1.56 (s, 9H), 1.23 (t, J=7.2 Hz, 3H).

Workup

  1. additionwere added
  2. customThe vial was sealed
  3. filtrationThe reaction mixture was filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. custompurified by preparative TLC (eluting with 12% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-a098abdc5b9a430d91501c17c08d13fd
Source dataset
uspto-grants-2016_02
Patent number
US09266886B2

Reaction notes

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