Sodium t-butoxide → HCID 178481621, compound

HRID 707321Notes

Reaction equation

HRID 707321 reaction equation
Cl[C:2]1[C:7]([N:8]([CH3:13])[C:9](=[O:12])OC)=[CH:6][C:5]([F:14])=[CH:4][N:3]=1.[S:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[NH:24][C@H:25]1[CH2:28][C@H:27]([NH2:29])[CH2:26]1.CC(C)([O-])C.[Na+]>[Pd+2]>[S:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[NH:24][C@H:25]1[CH2:26][C@H:27]([N:29]2[C:2]3=[N:3][CH:4]=[C:5]([F:14])[CH:6]=[C:7]3[N:8]([CH3:13])[C:9]2=[O:12])[CH2:28]1

Participants

5

Reactant 3

HCID 23676156Sodium t-butoxideHCID 86694180Methyl (2-chloro-5-fluoropyridin-3-yl)(methyl)carbamate2×HCID 178511738HCID 178511738, compound2×

Product 1

HCID 178481621HCID 178481621, compoundYield 56.3%

Reagents, catalysts & solvents 1

HCID 105144Allyl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)chloropalladium(II)Catalyst

Conditions

Temperature
50 °C

Procedure

Methyl (2-chloro-5-fluoropyridin-3-yl)(methyl)carbamate (intermediate 37, 0.310 g, 1.418 mmol), trans-N1-(benzo[d]thiazol-2-yl)cyclobutane-1,3-diamine (intermediate 11, 0.311 g, 1.418 mmol), chloro(2-dicyclohexylphosphino-3,6-dimethoxy-2′-4′-6′-tri-1-1,1′-biphenyl)]2-(2-aminoethyl)phenyl)palladium(ii) (0.085 g, 0.106 mmol), and sodium t-butoxide (0.341 g, 3.55 mmol) were scaled in a microwave vial under argon. Dry, sparged dioxane (1.5 mL) was added and the suspension heated at 50° C. After 20 minutes the vial was opened and the crude partitioned between 10% saturated ammonium chloride (100 mL) and ethyl acetate (200 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude was purified using silica chromatography (dichloromethane to ethyl acetate gradient) then triturated with diethyl ether. Filtration gave the desired 3-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-6-fluoro-1-methyl-1H-imidazo[4,5-b]pyridin-2(3H)-one (0.295 g, 0.799 mmol, 56.3% yield) as a free flowing cream colored solid. M+1: 370.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.44-2.59 (m, 2 H) 2.63 (s, 3 H) 3.46-3.56 (m, 2 H) 4.50-4.59 (m, 1 H) 5.31 (quin, J=8.20 Hz, 1 H) 7.03 (dd, J=8.02, 2.54 Hz, 1 H) 7.09 (td, J=7.58, 1.08 Hz, 1 H) 7.30 (td, J=7.73, 1.17 Hz, 1 H) 7.52 (dd, J=8.02, 0.39 Hz, 1 H) 7.60 (dd, J=7.82, 0.78 Hz, 1 H) 7.95 (t, J=2.15 Hz, 1 H).

Workup

  1. customDry
  2. customsparged dioxane (1.5 mL)
  3. additionwas added
  4. customthe crude partitioned between 10% saturated ammonium chloride (100 mL) and ethyl acetate (200 mL)
  5. dry with materialThe organic phase was dried with magnesium sulfate
  6. customevaporated to dryness under reduced pressure
  7. customThe crude was purified
  8. customthen triturated with diethyl ether
  9. filtrationFiltration

Sources & evidence

ORD record
ord-9503396a3cad4862b4242b865356afd9
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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