tert-Butyl methyl ether → HCID 178429374, compound

HRID 707309Notes

Reaction equation

HRID 707309 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([NH:15][C:16](=[O:27])[C:17]([C:20]2[C:21](Cl)=[N:22][CH:23]=[CH:24][CH:25]=2)([CH3:19])[CH3:18])[CH2:12]1.CC(C)([O-])C.[Na+].C(OC)(C)(C)C>>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([N:15]2[C:21]3=[N:22][CH:23]=[CH:24][CH:25]=[C:20]3[C:17]([CH3:19])([CH3:18])[C:16]2=[O:27])[CH2:12]1

Participants

4

Reactant 3

HCID 15413tert-Butyl methyl etherHCID 23676156Sodium t-butoxideHCID 178454574HCID 178454574, compound

Product 1

HCID 178429374HCID 178429374, compoundYield 58.6%

Conditions

Temperature
80 °C

Procedure

N-(Trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-2-(2-chloropyridin-3-yl)-2-methylpropanamide (0.086 g, 0.216 mmol), sodium t-butoxide (0.040 g, 0.416 mmol), and chloro(2-dicyclohexylphosphino-2′,6′-di-1-propoxy-1,1′-biphenyl)[2-(2-aminoethyl-phenyl)]palladium(ii), methyl t-butyl ether adduct (0.010 g, 0.012 mmol) were sealed in a microwave vessel under argon. Dry, sparged dioxane (0.5 mL) was added and the reaction heated at 80° C. After 35 minutes the mixture was cooled and partitioned between ethyl acetate (100 mL), water (100 mL) and saturated sodium bicarbonate (10 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (dichloromethane to ethyl acetate gradient) followed by reverse phase HPLC gave 1-(trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-3,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (0.0481 g, 0.126 mmol, 58.6% yield) as an off white solid. M+1: 365.1. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.39 (s, 6 H) 2.45 (m, J=3.36 Hz, 2 H) 3.38-3.63 (m, 2 H) 4.51-4.72 (m, 1 H) 5.30 (quin, J=8.66 Hz, 1 H) 5.59-5.80 (m, 1 H) 6.97 (dd, J=7.16, 5.26 Hz, 1 H) 7.04-7.16 (m, 1 H) 7.21-7.35 (m, 1 H) 7.43 (dd, J=7.31, 1.61 Hz, 1 H) 7.59 (dd, J=10.52, 8.33 Hz, 2 H) 8.19 (dd, J=5.19, 1.53 Hz, 1 H).

Workup

  1. customDry
  2. customsparged dioxane (0.5 mL)
  3. additionwas added
  4. temperatureAfter 35 minutes the mixture was cooled
  5. custompartitioned between ethyl acetate (100 mL), water (100 mL) and saturated sodium bicarbonate (10 mL)
  6. dry with materialThe organic phase was dried with magnesium sulfate
  7. customevaporated to dryness under reduced pressure
  8. customPurification

Sources & evidence

ORD record
ord-cf51434cec7440869ec1f6d1e542eaae
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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