Sodium t-butoxide → HCID 178481623, compound

HRID 707371Notes

Reaction equation

HRID 707371 reaction equation
Cl.[F:2][C:3]1[CH:17]=[CH:16][C:6]2[N:7]=[C:8]([NH:10][C@H:11]3[CH2:14][C@H:13]([NH2:15])[CH2:12]3)[S:9][C:5]=2[CH:4]=1.Cl[C:19]1[C:24]([N:25]([CH3:30])[C:26](=O)[O:27]C)=[CH:23][CH:22]=[CH:21][N:20]=1.CC(C)([O-])C.[Na+]>O1CCOCC1>[F:2][C:3]1[CH:17]=[CH:16][C:6]2[N:7]=[C:8]([NH:10][C@H:11]3[CH2:12][C@H:13]([N:15]4[C:19]5=[N:20][CH:21]=[CH:22][CH:23]=[C:24]5[N:25]([CH3:30])[C:26]4=[O:27])[CH2:14]3)[S:9][C:5]=2[CH:4]=1

Participants

5

Reactant 3

HCID 23676156Sodium t-butoxideHCID 86694230Methyl (2-chloropyridin-3-yl)(methyl)carbamateHCID 178479285HCID 178479285, compound

Product 1

HCID 178481623HCID 178481623, compoundYield 46.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

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
  2. additionThe residue was diluted with water
  3. extractionextracted with EtOAc
  4. extractionEtOAc extract
  5. concentrationwas concentrated
  6. customresidue purified with ISCO on silica gel column
  7. washeluting with 0-80% EtOAc/hexanes

Sources & evidence

ORD record
ord-c6b86a859f9e4e82837cbb73db54e320
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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