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

HRID 2275013Notes

Reaction equation

HRID 2275013 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:42])[NH:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:41])[C:30]2[CH:35]=[CH:34][C:33]([NH:36][CH3:37])=[C:32]([N+:38]([O-])=O)[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:42])[NH:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:29]([C:30]2[CH:35]=[CH:34][C:33]3[N:36]([CH3:37])[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:38][C:32]=3[CH:31]=2)=[O:41])[CH2:24]1)([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 3

HCID 24489Sodium DithioniteHCID 86340173HCID 86340173, compoundHCID 863401791,1-Dimethylethyl ((3R)-1-{[4-(methylamino)-3-nitrophenyl]carbonyl}-3-piperidinyl)carbamate

Product 1

HCID 118178623(R)-tert-Butyl(1-(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazole-5-carbonyl)piperidin-3-yl)carbamateYield 39.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (2 g, 8.99 mmol) in ethanol (90 mL) was added to a round bottom flask containing (R)-tert-butyl(1-(4-(methylamino)-3-nitrobenzoyl)piperidin-3-yl)carbamate (3.4 g, 8.98 mmol) and the resulting solution stirred at room temperature. A solution of sodium dithionite (3.14 g, 15.33 mmol) in water (45 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 and backwashed with water (2×100 ml). The organic layer was collected, dried with Na2SO4, filtered through a hydrophobic frit and concentrated under vacuum to yield a crude product. 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. This was dried under vacuum to yield the title compound as a yellow solid (1.867 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. customThe organic layer was collected
  9. dry with materialdried with Na2SO4
  10. filtrationfiltered through a hydrophobic frit
  11. concentrationconcentrated under vacuum
  12. customto yield a crude product
  13. custompurified
  14. washThe column was eluted with a gradient of 70-100% ethyl acetate in DCM for 10CV
  15. customAppropriate fractions were collected
  16. concentrationconcentrated under vacuum
  17. customThis was dried under vacuum

Sources & evidence

ORD record
ord-e2877024da094255a9395671e7e3ee82
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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