Potassium Phosphate, Tribasic → (S)-4-(2-((5-((2-Oxopyrrolidin-3-yl)amino)-1,3,4-oxadiazol-2-yl)methyl)benzo[d]thiazol-6-yl)benzamide

HRID 1754258Notes

Reaction equation

HRID 1754258 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)(=[O:3])[NH2:2].Br[C:14]1[CH:35]=[CH:34][C:17]2[N:18]=[C:19]([CH2:21][C:22]3[O:26][C:25]([NH:27][C@H:28]4[CH2:32][CH2:31][NH:30][C:29]4=[O:33])=[N:24][N:23]=3)[S:20][C:16]=2[CH:15]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.CO.[Pd]>[O:33]=[C:29]1[C@@H:28]([NH:27][C:25]2[O:26][C:22]([CH2:21][C:19]3[S:20][C:16]4[CH:15]=[C:14]([C:7]5[CH:8]=[CH:9][C:4]([C:1]([NH2:2])=[O:3])=[CH:5][CH:6]=5)[CH:35]=[CH:34][C:17]=4[N:18]=3)=[N:23][N:24]=2)[CH2:32][CH2:31][NH:30]1

Participants

9

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27378114-Aminocarbonylphenylboronic acidHCID 90047760(S)-3-((5-((6-Bromobenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)amino)pyrrolidin-2-one

Product 1

HCID 90047667(S)-4-(2-((5-((2-Oxopyrrolidin-3-yl)amino)-1,3,4-oxadiazol-2-yl)methyl)benzo[d]thiazol-6-yl)benzamideYield 31.9%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

To a microwave vial containing SiliaCat DPP-Pd (150 mg, 0.041 mmol) and (4-carbamoylphenyl)boronic acid (65 mg, 0.40 mmol) were added Compound 51b (104 mg, 0.260 mmol) dissolved in dioxane (2.5 mL) followed by K3PO4 (138 mg, 0.79 mmol) dissolved in water (0.3 mL) and the reaction mixture was heated in a microwave reactor at 125° C. for 1.5 h. The reaction mixture was allowed to cool to rt then diluted with a mixture of DCM and MeOH, filtered and concentrated under reduced pressure. The residue was purified on silica gel eluting with 0 to 15% MeOH/DCM to give Compound 51c (36 mg, 31% yield) as a pale brown solid. LCMS=1.33 min using analytical method (B), 435.1 (M+H). 1H NMR (400 MHz CDCl3 containing CD3OD) δ 8.05 (d, J=1.5 Hz, 1H), 7.98 (d, J=8.5 Hz, 1H), 7.89 (d, J=8.5 Hz, 2H), 7.69 (dd, J=8.5, 1.8 Hz, 1H), 7.65 (d, J=8.5 Hz, 2H), 4.54 (s, 1H), 4.23 (dd, J=10.5, 8.3 Hz, 1H), 3.36-3.31 (m, 1H), 2.68-2.59 (m, 1H), 2.03 (dq, J=12.5, 9.8 Hz, 1H).

Workup

  1. temperatureto cool to rt
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified on silica gel eluting with 0 to 15% MeOH/DCM

Sources & evidence

ORD record
ord-bd3ba0e94b354749bebceb24e282a52f
Source dataset
uspto-grants-2015_10
Patent number
US09169240B2

Reaction notes

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