Hydrochloric Acid → 6-Fluoro-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine hydrochloride

HRID 131343Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:17]([O-])=O)=[C:6]([NH:8][C:9]2[S:10][C:11]([CH3:16])=[CH:12][C:13]=2[C:14]#[N:15])[CH:7]=1.Cl.[Sn](Cl)[Cl:22]>CCO>[ClH:22].[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:17]=[C:14]([NH2:15])[C:13]3[CH:12]=[C:11]([CH3:16])[S:10][C:9]=3[NH:8][C:6]=2[CH:7]=1

Participants

Conditions

Temperature: 85 °C

Procedure

Stir 2-(5-fluoro-2-nitro-phenylamino)-5-methyl-thiophene-3-carbonitrile (113 g, 0.408 mol) as a suspension in EtOH (1.1 L) at ambient temperature. Add aqueous 6N HCl (1.1 L) and tin (II) chloride (232 g, 1.22 mol) with stirring. Heat to gentle reflux (85° C.) for 3-4 hours, and then allow cooling to ambient temperature. Filter the crude product and rinse with 1:1/EtOH:6N HCl, then deionized water, and dry in a vacuum oven at 50° C. to constant weight. Stir the crude product (139 g) as a suspension in aqueous 1N HCl (6 L) at gentle reflux (95° C.) for 2 hours, and then allow cooling to ambient temperature. Filter the product and rinse with 1N HCl and water, then dry at 50° C. to give 101 g (87%) the title compound: 1H NMR (400 MHz, DMSO-d6) δ 11.33 (bs, 1H), 9.80 (s, 1H), 9.16 (bs, 1H), 8.88 (bs, 1H), 6.99 (m, 1H), 6.89 (m, 1H), 6.84 (s, 1H), 2.28 (s, 3H). HRMS (ES) exact mass M+H calcd for C12H11ClFN3S 248.0658; found 248.0657.

Workup

temperatureHeat
temperatureallow cooling to ambient temperature
filtrationFilter the crude product
washrinse with 1:1/EtOH
customdry in a vacuum oven at 50° C. to constant weight
temperatureat gentle reflux (95° C.) for 2 hours
temperatureallow cooling to ambient temperature
filtrationFilter the product
washrinse with 1N HCl and water
customdry at 50° C.

Sources & evidence

ORD record: ord-db0bb8e5d99649ad818994a19b9ff6f7
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07384934B2

Reaction notes

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