Riluzole → 3-(Trifluoromethoxy)aniline

HRID 1966051Notes

Reaction equation

HRID 1966051 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:7][C:5]=2[N:6]=1.FC(F)(F)C1C=CC([NH2:22])=CC=1.FC(F)(F)C1C=C(C=CC=1)N.[CH3:38][S:39](C1C=CC(N)=CC=1)(=[O:41])=[O:40].Cl.CS(C1C=C(C=CC=1)N)(=O)=O.CS(C1C=C(C=CC=1)N)(=O)=O.FC(F)(F)OC1C=CC(N)=CC=1.ClC1C=CC=CC=1O.CS(C1C=CC2N=C(N)SC=2C=1)(=O)=O.[S-]C#N.CSC1C=C(C=CC=1)N>>[F:13][C:12]([F:15])([F:14])[O:11][C:9]1[CH:10]=[C:4]([CH:5]=[CH:7][CH:8]=1)[NH2:22].[CH3:38][S:39]([C:8]1[CH:9]=[CH:10][C:4]2[S:3][C:2]([NH2:1])=[N:6][C:5]=2[CH:7]=1)(=[O:41])=[O:40]

Participants

13

Reactant 11

HCID 5070RiluzoleHCID 72452-ChlorophenolHCID 73753-(Trifluoromethyl)anilineHCID 9322ThiocyanateHCID 99644-(Trifluoromethyl)anilineHCID 15693Benzenamine, 3-(methylthio)-HCID 796174-(Methylsulfonyl)anilineHCID 871522-Benzothiazolamine, 6-(methylsulfonyl)-HCID 4280293-(Methylsulphonyl)aniline2×HCID 6008484-(Trifluoromethoxy)anilineHCID 27351793-(Methylsulfonyl)aniline hydrochloride

Product 2

HCID 737533-(Trifluoromethoxy)anilineHCID 1085169HCID 1085169, compound

Procedure

The reaction may be conducted in acetonitrile in the presence of benzyltrimethylammonium tribromide (similar to J. Organic Chemistry, 2003, 68, 8693). Alternatively, potassium thiocyanate may be used (similar to Journal of Medicinal Chemistry, 49(2), 664-677; 2006 see also Tetrahedron, 42(20), 5739-46; 1986). The reaction proceeds with good yield, both in the case where the aniline is 4-substituted and 3-substituted, giving rise to 6 and 5-substituted 2-amino-benzothiazoles respectively. 2-amino-6-trifluoromethoxybenzothiazole (RN: 850608-87-6) is a commercially available compound. 4-Trifluoromethylaniline (RN: 455-14-1), 3-trifluoromethylaniline (RN: 9-16-8), 4-methanesulphonylaniline (5470-49-5), 3-methansulphonylaniline hydrochloride (RN: 80213-28-1), 3-methanesulphonylaniline (RN: 352116-39-8), just like 4-trifluoromethoxy aniline (RN: 1535-73-5) are compounds that are commercially available. 3-Trifluoromethoxyaniline (RN: 1535-73-5) is prepared starting from 2-chlorophenol as described in Bulletin de la Societe Chimique de France, (6), 925-9; 1986. 3-Methanesulphonylaniline may also be prepared by nitration of the sulphone followed by reduction of the nitro group, as described in Helvetica Chimica Acta (1981), 64(6), 1849-53. 6-Methanesulphonyl-2-aminobenzothiazole may also be prepared by oxidation of the corresponding 6-thio-methylether-N-BOC-benzoimidazole obtained by reacting with thiocyanate as described above, starting from the commercially available compound 3-methylthioaniline (RN: 1783-81-9). Similar, the corresponding 5-methanesulphonyl-2-aminobenzothiazole may be obtained. The 2-aminobenzothiazoles substituted at positions 5 and 6, described in this invention, may also be obtained by reacting the appropriately substituted 2-thioanilines with bis-carboimidoyl-imidazole (RN: 104619-51-4), similar to as described in Journal of Heterocyclic Chemistry, 40(1), 191-193; 2003, as reported in Scheme 4:

Workup

  1. customobtained

Sources & evidence

ORD record
ord-a7a3aa8b44fa4398854bfc1f4e22a0fc
Source dataset
uspto-grants-2013_04
Patent number
US08420634B2

Reaction notes

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