Sodium Dithionite → (R)-tert-Butyl(1-(7-methoxy-1-methyl-2-(1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carbonyl)piperidin-3-yl)carbamate

HRID 2275016Notes

Reaction equation

HRID 2275016 reaction equation
[C:1]([O:5][C:6](=[O:29])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:28])[C:15]2[CH:20]=[C:19]([N+:21]([O-])=O)[C:18]([NH:24][CH3:25])=[C:17]([O:26][CH3:27])[CH:16]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[F:30][C:31]([F:45])([F:44])[CH2:32][N:33]1[C:37]2=[N:38][CH:39]=[CH:40][CH:41]=[C:36]2[CH:35]=[C:34]1[CH:42]=O.S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O.C(Cl)Cl>[C:1]([O:5][C:6](=[O:29])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([C:15]2[CH:16]=[C:17]([O:26][CH3:27])[C:18]3[N:24]([CH3:25])[C:42]([C:34]4[N:33]([CH2:32][C:31]([F:45])([F:44])[F:30])[C:37]5=[N:38][CH:39]=[CH:40][CH:41]=[C:36]5[CH:35]=4)=[N:21][C:19]=3[CH:20]=2)=[O:28])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 24489Sodium DithioniteHCID 86340183(R)-tert-Butyl (1-(3-methoxy-4-(methylamino)-5-nitrobenzoyl)piperidin-3-yl)carbamateHCID 900283341-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde

Product 1

HCID 118178624(R)-tert-Butyl(1-(7-methoxy-1-methyl-2-(1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-benzo[d]imidazole-5-carbonyl)piperidin-3-yl)carbamateYield 83.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-tert-butyl(1-(3-methoxy-4-(methylamino)-5-nitrobenzoyl)piperidin-3-yl)carbamate (3.58 g, 8.76 mmol) and 1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (2.61 g, 11.44 mmol) in ethanol (140 ml) was added portionwise a solution of sodium hydrosulfite (3.18 g, 15.53 mmol) in water (70 ml). The mixture was flushed with nitrogen then heated at 100° C. overnight (16 hours). The reaction mixture was concentrated under vacuum then diluted with DCM (150 ml) and water (150 ml). The organic layer was collected and the aqueous layer washed with DCM (3×100 ml). Organic layers were collected, dried with Na2SO4, filtered through a hydrophobic frit and concentrated under vacuum to yield 5.5 g of crude product as white solid. This was dissolved in a minimum volume of DCM and purified using Biotage SP4 on a 100 g SNAP silica cartridge. The column was eluted with a gradient of 70-100% ethyl acetate in DCM for 10CV. Appropriate fractions were collected and concentrated under vacuum to yield the title compound as a white solid (4.31 g).

Workup

  1. customThe mixture was flushed with nitrogen
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. additionthen diluted with DCM (150 ml) and water (150 ml)
  4. customThe organic layer was collected
  5. washthe aqueous layer washed with DCM (3×100 ml)
  6. customOrganic layers were collected
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered through a hydrophobic frit
  9. concentrationconcentrated under vacuum
  10. customto yield 5.5 g of crude product as white solid
  11. custompurified
  12. washThe column was eluted with a gradient of 70-100% ethyl acetate in DCM for 10CV
  13. customAppropriate fractions were collected
  14. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-96cd6732cb984dddaa577ceffe2d081a
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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