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

HRID 2275017Notes

Reaction equation

HRID 2275017 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3=[N:10][CH:11]=[CH:12][CH:13]=[C:8]3[CH:7]=[C:6]2[CH:14]=O)[CH2:3][CH2:2]1.[C:16]([O:20][C:21](=[O:44])[NH:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:43])[C:30]2[CH:35]=[C:34]([N+:36]([O-])=O)[C:33]([NH:39][CH3:40])=[C:32]([O:41][CH3:42])[CH:31]=2)[CH2:24]1)([CH3:19])([CH3:18])[CH3:17].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O.C(Cl)Cl>[C:16]([O:20][C:21](=[O:44])[NH:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:29]([C:30]2[CH:31]=[C:32]([O:41][CH3:42])[C:33]3[N:39]([CH3:40])[C:14]([C:6]4[N:5]([CH2:4][CH:1]5[CH2:2][CH2:3]5)[C:9]5=[N:10][CH:11]=[CH:12][CH:13]=[C:8]5[CH:7]=4)=[N:36][C:34]=3[CH:35]=2)=[O:43])[CH2:24]1)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 3

HCID 24489Sodium DithioniteHCID 86340173HCID 86340173, compoundHCID 86340183(R)-tert-Butyl (1-(3-methoxy-4-(methylamino)-5-nitrobenzoyl)piperidin-3-yl)carbamate

Product 1

HCID 118178622(R)-tert-Butyl(1-(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazole-5-carbonyl)piperidin-3-yl)carbamateYield 74.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (0.743 g, 3.71 mmol) in ethanol (60 mL) was added to a round bottom flask containing (R)-tert-butyl(1-(3-methoxy-4-(methylamino)-5-nitrobenzoyl)piperidin-3-yl)carbamate (1.529 g, 3.74 mmol) and the resulting solution stirred at room temperature. A solution of sodium dithionite (1.375 g, 6.71 mmol) in water (30 mL) was added portionwise to the reaction mixture. The reaction mixture was heated to 100° C. and stirred under nitrogen for 4 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 2 g of crude product as yellow solid. This was dissolved in a minimum volume of DCM and purified using Biotage SP4 on a 50 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 yellow solid (1.55 g).

Workup

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

Sources & evidence

ORD record
ord-edccad7d35764f61bf428fd994e82ffe
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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