Sodium Carbonate → HCID 66668197, compound

HRID 2176433Notes

Reaction equation

HRID 2176433 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[S:30][C:11]3=[N:12][C:13]([N:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]4)=[CH:14][C:15](=[O:16])[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[N:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:16]=[C:15]1[N:10]2[N:9]=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:34]4[CH:35]=[CH:36][N:31]=[CH:32][CH:33]=4)[CH:3]=3)[S:30][C:11]2=[N:12][C:13]([N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:14]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 66668263HCID 66668263, compound

Product 1

HCID 66668197HCID 66668197, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of tert-butyl 4-(2-(3-bromophenyl)-5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate (40 mg, 0.081 mmol, 1.0 equiv) in 1 mL DMF, 0.5 mL ethanol and 0.25 mL water in a microwave vial is added 4-pyridineboronic acid (19.97 mg, 0.162 mmol, 2.0 equiv), sodium carbonate (25.8 mg, 0.244 mmol, 3.0 equiv), and tetrakis(triphenylphosphine)palladium(0) (4.69 mg, 4.06 μmol, 0.05 equiv). The mixture is heated in a microwave reactor for 30 min at 120° C. Upon completion the mixture is filtered through a thiol-SPE column (Stratospheres) and the resulting solution is concentrated in vacuo to give crude tert-butyl 4-(5-oxo-2-(3-(pyridin-4-yl)phenyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-7-yl)piperazine-1-carboxylate as a yellow oil. The residue is then taken on crude to the next reaction, which follows the same deprotection procedure as described in Step 3 of Example 1 to give 7-(piperazin-1-yl)-2-(3-(pyridin-4-yl)phenyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (12 mg, 38%) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.67 (dd, J=4.30, 1.57 Hz, 2H), 8.18 (s, 1H), 8.02 (dd, J=16.43, 8.22 Hz, 2H), 7.70-7.82 (m, 3H), 5.40 (s, 1H), 3.42-3.51 (m, 4H), 2.68-2.75 (m, 4H); LCMS: (electrospray+ve), m/z 391.1 (MH)+; HPLC: tR=2.82 min, UV254=100%. HRMS (ESI): m/z calcd for C20H19N6OS [M+H]+391.1321. found 391.1322.

Workup

  1. filtrationUpon completion the mixture is filtered through a thiol-SPE column (Stratospheres)
  2. concentrationthe resulting solution is concentrated in vacuo

Sources & evidence

ORD record
ord-4bbbabe71c72417784a02b4faf75f225
Source dataset
uspto-grants-2015_06
Patent number
US09066948B2

Reaction notes

Loading…