Sodium Dithionite → (R)-tert-Butyl(1-(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 2275012Notes

Reaction equation

HRID 2275012 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:26])[C:15]2[CH:20]=[CH:19][C:18]([NH:21][CH3:22])=[C:17]([N+:23]([O-])=O)[CH:16]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[F:28][C:29]([F:43])([F:42])[CH2:30][N:31]1[C:35]2=[N:36][CH:37]=[CH:38][CH:39]=[C:34]2[CH:33]=[C:32]1[CH:40]=O.S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O>[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([C:15]2[CH:20]=[CH:19][C:18]3[N:21]([CH3:22])[C:40]([C:32]4[N:31]([CH2:30][C:29]([F:43])([F:42])[F:28])[C:35]5=[N:36][CH:37]=[CH:38][CH:39]=[C:34]5[CH:33]=4)=[N:23][C:17]=3[CH:16]=2)=[O:26])[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 24489Sodium DithioniteHCID 863401791,1-Dimethylethyl ((3R)-1-{[4-(methylamino)-3-nitrophenyl]carbonyl}-3-piperidinyl)carbamateHCID 900283341-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde

Product 1

HCID 118178621(R)-tert-Butyl(1-(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 62.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of (R)-tert-butyl(1-(4-(methylamino)-3-nitrobenzoyl)piperidin-3-yl)carbamate (2.1 g, 5.55 mmol) and 1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (1.3 g, 5.70 mmol) in ethanol (55 ml) was added portionwise a solution of sodium hydrosulfite (3.41 g, 16.65 mmol) in water (25 ml). The mixture was flushed with nitrogen and heated at 90° C. overnight for 17 hours. The reaction mixture was allowed to cool to room temperature and the solvent was evaporated in vacuo. DCM was added to the residue and the heterogeneous solution was dried over sodium sulfate. The solid was filtered off and the filtrate was concentrated under vacuo. The residue was loaded in dichloromethane and purified by SP4 SNAP on 2 silica (Si) 100 g columns using an initial gradient of 25-80% (15 CVs), followed by 80-100% (10 CVs) ethyl acetate/cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a pale yellow solid (1.934 g).

Workup

  1. customThe mixture was flushed with nitrogen
  2. temperatureto cool to room temperature
  3. customthe solvent was evaporated in vacuo
  4. additionDCM was added to the residue
  5. dry with materialthe heterogeneous solution was dried over sodium sulfate
  6. filtrationThe solid was filtered off
  7. concentrationthe filtrate was concentrated under vacuo
  8. custompurified by SP4 SNAP on 2 silica (Si) 100 g columns
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-a114b876e6564a09bb6c503b9c81b45d
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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