Sodium t-butoxide → HCID 178429375, compound

HRID 707287Notes

Reaction equation

HRID 707287 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:25](Cl)=[N:24][CH:23]=[CH:22][N:21]=2)([CH3:19])[CH3:18])[CH2:12]1.CC(C)([O-])C.[Na+]>CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.CC(OC)(C)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O1CCOCC1>[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:25]3=[N:24][CH:23]=[CH:22][N:21]=[C:20]3[C:17]([CH3:19])([CH3:18])[C:16]2=[O:27])[CH2:12]1

Participants

5

Reactant 2

HCID 23676156Sodium t-butoxideHCID 178454575HCID 178454575, compound

Product 1

HCID 178429375HCID 178429375, compoundYield 48.2%

Reagents, catalysts & solvents 2

HCID 66572931HCID 66572931, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a glass microwave reaction vessel was added N-(cis-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)-2-(3-chloropyrazin-2-yl)-2-methylpropanamide (0.3181 g, 0.791 mmol), RuPhos Precatalyst (0.035 g, 0.047 mmol, Strem Chemicals, Inc.), and sodium tert-butoxide (0.152 g, 1.583 mmol, Sigma-Aldrich Chemical Company, Inc.) in dry dioxane (0.791 ml) to stir at 80° C. for 5 h. The crude product was purified by reverse-phase preparative HPLC using 0.1% TFA in CH3CN/H2O, gradient 10% to 90% over 12 mins. The collected fractions were evaporated and the residue was taken up in DCM and filtered through a Silicycle Si-Carbonate cartridge to remove any salts to give the title compound (139.2 mg, 0.381 mmol, 48.1% yield). LCMS showed product peak at 1.607 min (m+1=366.0). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.35 (s, 6 H) 2.74 (qd, J=7.86, 2.64 Hz, 2 H) 3.00 (qd, J=9.13, 2.74 Hz, 2 H) 4.12-4.27 (m, 1 H) 4.55-4.69 (m, 1 H) 7.04 (td, J=7.58, 1.08 Hz, 1 H) 7.24 (td, J=7.68, 1.27 Hz, 1 H) 7.36-7.44 (m, 1 H) 7.69 (dd, J=7.83, 0.78 Hz, 1 H) 8.15-8.23 (m, 2 H) 8.49 (d, J=6.65 Hz, 1 H)

Workup

  1. customTo a glass microwave reaction vessel
  2. customThe crude product was purified by reverse-phase preparative HPLC
  3. customover 12 mins
  4. customThe collected fractions were evaporated
  5. filtrationfiltered through a Silicycle Si-Carbonate cartridge
  6. customto remove any salts

Sources & evidence

ORD record
ord-eb88e19f5fd54ef9b092aecfb43b83f0
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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