Hydrochloric Acid → HCID 178479285, compound

HRID 707370Notes

Reaction equation

HRID 707370 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:11][C@H:10]([NH:12][C:13]2[S:14][C:15]3[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:16]=3[N:17]=2)[CH2:9]1)(C)(C)C.[ClH:24].O1CCOCC1>>[ClH:24].[F:22][C:20]1[CH:19]=[CH:18][C:16]2[N:17]=[C:13]([NH:12][C@H:10]3[CH2:9][C@H:8]([NH2:7])[CH2:11]3)[S:14][C:15]=2[CH:21]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 178454114HCID 178454114, compound

Product 1

HCID 178479285HCID 178479285, compound

Procedure

A mixture of tert-butyl(trans-3-aminocyclobutyl)carbamate (0.099 g, 0.533 mmol), 2-chloro-6-fluoro-1,3-benzothiazole (0.100 g, 0.533 mmol) and diisopropylethylamine (0.185 ml, 1.066 mmol) in DMSO (0.5 mL) contained in a microwave vial was capped and heated to 120° C. for 2 hrs. The mixture was diluted with water and extracted with EtOAc. EtOAc extract was concentrated to give crude tert-butyl(trans-3-((6-fluorobenzo[d]thiazol-2-yl)amino)cyclobutyl)carbamate. To the crude tert-butyl(trans-3-((6-fluorobenzo[d]thiazol-2-yl)amino)cyclobutyl)carbamate was added hydrogen chloride, 4N in 1,4-dioxane (10 ml, 40.0 mmol) and the resulting solution stirred at room temperature for 2 h and concentrated to afford crude trans-N1-(6-fluorobenzo[d]thiazol-2-yl)cyclobutane-1,3-diamine hydrochloride. The crude trans-N1-(6-fluorobenzo[d]thiazol-2-yl)cyclobutane-1,3-diamine hydrochloride was added to mixture of methyl (2-chloropyridin-3-yl)(methyl)carbamate, INTERMEDIATE 40, (0.107 g, 0.533 mmol), chloro(2-dicyclohexylphosphino-3,6-dimethoxy-2′-4′-6′-triisopropyl-1,1′-biphenyl)]2-(2-aminoethyl)Ph)Pd(II) (0.021 g, 0.027 mmol), and sodium tert-butoxide (0.261 ml, 2.132 mmol) in dioxane (10 mL). The mixture was stirred at 100° C. for 2 h and concentrated. The residue was diluted with water and extracted with EtOAc. EtOAc extract was concentrated and residue purified with ISCO on silica gel column eluting with 0-80% EtOAc/hexanes to give the title compound 3-(trans-3-((6-fluorobenzo[d]thiazol-2-yl)amino)cyclobutyl)-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one (0.092 g, 0.249 mmol, 46.7% yield). m/z: 370.1 (M+1); 1H NMR (400 MHz, CHLOROFORM-d) δ: ppm 8.07 (dd, J=5.18, 1.27 Hz, 1 H), 7.49 (dd, J=8.90, 4.79 Hz, 1 H), 7.32 (dd, J=8.12, 2.64 Hz, 1 H), 7.17 (dd, J=7.73, 1.27 Hz, 1 H), 6.97-7.07 (m, 2 H), 5.90 (br. s., 1 H), 5.33-5.50 (m, 1 H), 4.48-4.74 (m, 1 H), 3.48-3.67 (m, 2 H), 3.43 (s, 3 H), 2.34-2.63 (m, 2 H).

Workup

  1. concentrationconcentrated

Sources & evidence

ORD record
ord-3590e229c6d246bcb776168522b6af45
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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