Sodium Dithionite → HCID 58344958, compound

HRID 1887991Notes

Reaction equation

HRID 1887991 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N+:24]([O-])=O)[C:5]([NH:8][C:9]2[CH:23]=[CH:22][C:12]([CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[NH2:27][C:28]1[N:35]=[CH:34][CH:33]=[CH:32][C:29]=1[CH:30]=O.S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.O.ClCCl.CO.CS(C)=O>[NH2:27][C:28]1[C:29]([C:30]2[N:8]([C:9]3[CH:23]=[CH:22][C:12]([CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:11][CH:10]=3)[C:5]3=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=[C:4]3[N:24]=2)=[CH:32][CH:33]=[CH:34][N:35]=1

Participants

9

Reactant 3

HCID 24489Sodium DithioniteHCID 7376333-Pyridinecarboxaldehyde, 2-amino-HCID 60155004HCID 60155004, compound

Product 1

HCID 58344958HCID 58344958, compoundYield 41%

Reagents, catalysts & solvents 5

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

tert-butyl 4-((5-bromo-3-nitropyridin-2-yl)amino)benzylcarbamate (25.0 g, 58.9 mmol), 2-aminonicotinaldehyde (10.2 g, 83.5 mmol), sodium dithionite (31.0 g, 178 mmol), methanol (80 mL), and DMSO (500 mL) were placed in a round-bottomed flask which was allowed to stir at 100° C. for 36 h. After cooling to room temperature the mixture was diluted with ethyl acetate (500 mL) and water (500 mL). The layers were separated, the organic layer was washed with water (2×300 mL) and concentrated to yield the crude product as a black oily solid (29.2 g). Column chromatography (1-5% methanol in dichloromethane) yielded an orange solid which could be further purified by re-crystallization (ethyl acetate/hexanes, 1:1) to yield tert-butyl 4-(2-(2-aminopyridin-3-yl)-6-bromo-3H-imidazo[4,5-b]pyridine-3-yl)benzylcarbamate (11.8 g, 23.8 mmol, 41%) as an off-white solid. Mp. 176-178° C.; 400 M Hz 1H NMR (DMSO-d6) δ: 8.50 (d, J=2.0 Hz, 1H), 8.40 (d, J=2.4 Hz, 1H), 7.99 (dd, J=2.0 Hz and 4.7 Hz, 1H), 7.48 (t, J=5.6 Hz, 1H), 7.40-7.31 (m, 3H), 7.23 (dd, J=2.0 Hz and 7.8 Hz, 1H), 6.97 (s, 2H), 6.40 (dd, J=4.4 Hz and 7.7 Hz, 1H), 4.121 (d, J=6.2 Hz, 2H), 1.41 (s, 9H), MS 495.34, 497.23 [M+H, M+2+H].

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. customThe layers were separated
  3. washthe organic layer was washed with water (2×300 mL)
  4. concentrationconcentrated
  5. customto yield the crude product as a black oily solid (29.2 g)
  6. customcould be further purified by re-crystallization (ethyl acetate/hexanes, 1:1)

Sources & evidence

ORD record
ord-e0012d1d22d34a3cb1eac42e1f63ac65
Source dataset
uspto-grants-2013_08
Patent number
US08501770B2

Reaction notes

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