Ammonium formate → tert-Butyl (4-amino-2-cyanophenyl)carbamate

HRID 62101Notes

Reaction equation

HRID 62101 reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-])=O)[CH:6]=[CH:5][C:4]=1[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])#[N:2].C([O-])=O.[NH4+]>C(O)C.[Pd]>[NH2:9][C:7]1[CH:6]=[CH:5][C:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[C:3]([C:1]#[N:2])[CH:8]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 65142565HCID 65142565, compound

Product 1

HCID 43548909tert-Butyl (4-amino-2-cyanophenyl)carbamate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

The thiazolo[5,4-f]quinazoline-2-carbonitriles VIIIaa-ib were prepared following scheme 1: N-Boc Protection of 2-amino-5-nitrobenzonitrile using di-tert-butyl dicarbonate in a suitable solvent, such as dichloromethane, in presence of suitable bases such as triethylamine and 4-(dimethylamino)pyridine and preferably at room temperature, provides tert-butyl (2-cyano-4-nitrophenyl)carbamate I in high yield. Reduction of the nitro intermediate I, for example by treatment with ammonium formate and a catalytic amount of 10% palladium charcoal preferably in ethanol under microwave irradiation for preferably 30 min at 600 W, provides tert-butyl 4-amino-2-cyanophenylcarbamate II in high yield. Treatment of intermediate II by a solution of bromine in dichloromethane in a suitable solvent, such as acetic acid, preferably at room temperature provides tert-butyl 4-amino-3-bromo-2-cyanophenylcarbamate III in a quantitative yield. Intermediate III is reacted with Appel's salt (4,5-dichloro-1,2,3-dithiazolium chloride) (Appel, R. et al., Chem. Ber., 1985, 118, 1632) preferably in dichloromethane at room temperature to afford (Z)-tert-butyl-3-bromo-4-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)-2-cyanophenylcarbamate IV. N-Boc deprotection of intermediate IV using di-tert-butyl dicarbonate in a suitable solvent, such acetic acid, preferably under microwave irradiation at 118° C. provides (Z)-6-amino-2-bromo-3-(4-chloro-5H-1,2,3-dithiazol-5-ylideneamino)benzonitrile V in a quantitative yield. Cyclization of intermediate V may be accomplished by treatment with copper iodide in a suitable solvent, such as pyridine, preferably under microwave irradiation at 400 W at 130° C. for 20 min to obtain 6-aminobenzo[d]thiazole-2,7-dicarbonitrile VI in good yield (Besson, T. et al., J. Chem. Soc., Perkin Trans. 1, 1998, 3925). Treatment of intermediate VI in a suitable solvent, such as dimethylformamide dimethylacetal, preferably under microwave irradiation at 70° C. (600 W) gives (E)-N′-(2,7-dicyanobenzo[d]thiazol-6-yl)-N,N-dimethylformimidamide VII in good yield. Cyclization of intermediate VII in thiazolo[5,4-f]quinazoline-2-carbonitriles VIIIaa-ib may be accomplished by a Dimroth rearrangement using the appropriate aniline or primary amine R3NH2 (preferably 1.5 equivalent) in a suitable solvent, such acetic acid and preferably under microwave irradiation at 118° C. (600 W) (Foucourt, A. et al., Tetrahedron, 2010, 66, 4495).

Workup

  1. customfor preferably 30 min

Sources & evidence

ORD record
ord-441da470e92147b9966b3a5f8e99eb4f
Source dataset
uspto-grants-2016_09
Patent number
US09446044B2

Reaction notes

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