Sodium Dithionite → (4-{6-Bromo-7-[4-(thiazol-2-ylcarbamoylmethyl)-piperazin-1-yl]-3H-imidazo[4,5-b]pyridin-2-yl}-benzyl)-carbamic acid tert-butyl ester

HRID 416703Notes

Reaction equation

HRID 416703 reaction equation
[NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]([NH:20][C:21]3[S:22][CH:23]=[CH:24][N:25]=3)=[O:19])[CH2:13][CH2:12]2)[C:5]([Br:26])=[CH:4][N:3]=1.[CH:27]([C:29]1[CH:43]=[CH:42][C:32]([CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:31][CH:30]=1)=O.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(O)C>[C:37]([O:36][C:35](=[O:41])[NH:34][CH2:33][C:32]1[CH:31]=[CH:30][C:29]([C:27]2[NH:1][C:2]3=[N:3][CH:4]=[C:5]([Br:26])[C:6]([N:11]4[CH2:16][CH2:15][N:14]([CH2:17][C:18](=[O:19])[NH:20][C:21]5[S:22][CH:23]=[CH:24][N:25]=5)[CH2:13][CH2:12]4)=[C:7]3[N:8]=2)=[CH:43][CH:42]=1)([CH3:40])([CH3:39])[CH3:38]

Participants

5

Reactant 3

HCID 24489Sodium DithioniteHCID 2794832tert-Butyl hydrogen ((4-formylphenyl)methyl)carbonimidateHCID 468678032-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide

Product 1

HCID 178453035(4-{6-Bromo-7-[4-(thiazol-2-ylcarbamoylmethyl)-piperazin-1-yl]-3H-imidazo[4,5-b]pyridin-2-yl}-benzyl)-carbamic acid tert-butyl esterYield 35.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-[4-(2-amino-5-bromo-3-nitro-pyridin-4-yl)-piperazin-1-yl]-N-thiazol-2-yl-acetamide (0.1 g, 0.22 mmol) and ethanol (5 ml) was added tert-butyl N-(4 formylbenzyl)carbamate (69 mg, 0.29 mmol) and a freshly prepared aqueous solution of Na2S2O4 (1M; 900 μL, 0.9 mmol). The reaction mixture was stirred at 80° C. for 16 h then concentrated in vacuo. The crude product was purified by chromatography on silica gel (dichloromethane/ethyl acetate 7:3+0.5% methanol to 2% methanol in ethyl acetate). The isolated product was further triturated in ether/methanol 9:1, filtered, and dried in vacuo to give the title compound as a pale yellow solid (0.049 g, 34%);

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe crude product was purified by chromatography on silica gel (dichloromethane/ethyl acetate 7:3+0.5% methanol to 2% methanol in ethyl acetate)
  3. customThe isolated product was further triturated in ether/methanol 9:1
  4. filtrationfiltered
  5. customdried in vacuo

Sources & evidence

ORD record
ord-cb934d6baa92421799bd8d7ce6722317
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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