Sodium Carbonate → 6-(5-(Methylthio)-1,3,4-thiadiazol-2-yl)isoquinoline

HRID 2075341Notes

Reaction equation

HRID 2075341 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][C:7](B(O)O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.Br[C:15]1[S:16][C:17]([S:20][CH3:21])=[N:18][N:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.C(COC)OC>[CH3:21][S:20][C:17]1[S:16][C:15]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[CH:1]=[N:2][CH:3]=[CH:4]3)=[N:19][N:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 222696212-Bromo-5-(methylsulfanyl)-1,3,4-thiadiazoleHCID 44119669(Isoquinolin-6-yl)boronic acid

Product 1

HCID 579918536-(5-(Methylthio)-1,3,4-thiadiazol-2-yl)isoquinolineYield 95%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred mixture or isoquinolin-6-ylboronic acid (83 mg, 0.33 mmol) (prepared as described in US Patent Publication No. US 2007/0173506), 2-bromo-5-(methylthio)-1,3,4-thiadiazole (82 mg, 0.39 mmol) (prepared as described in WO 97/30981) and Pd(PPh3)4 (19 mg, 0.016 mmol) was added dimethoxyethane (5.0 mL) and sodium carbonate (0.41 mM, 2.0 M aq, 0.82 mmol). The mixture was heated at 90° C. under a reflux condenser overnight. After cooling, the mixture was filtered through a short path of Celite and washed with EtOAc (3×10 mL). The combined organic layers were evaporated and purified by flash column chromatography (eluting with a gradient of 1:1 EtOAc in hexanes to pure EtOAc) to provide 6-(5-(methylthio)-1,3,4-thiadiazol-2-yl)isoquinoline (80 mg, 95%) as a pale yellow solid. LCMS (M+H) 260.4 calc. for C12H10N3S2 260.0. 1H NMR (400 MHz, CDCl3): δ ppm 9.33 (d, J=1.17 Hz, 1H) 8.62 (s, 1H) 8.31 (s, 1H) 8.23 (d, J=8.80 Hz, 1H) 8.11 (d, J=8.80 Hz, 1H) 7.74-7.83 (m, 1H) 2.88 (s, 3H).

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered through a short path of Celite
  3. washwashed with EtOAc (3×10 mL)
  4. customThe combined organic layers were evaporated
  5. custompurified by flash column chromatography (
  6. washeluting with a gradient of 1:1 EtOAc in hexanes to pure EtOAc)

Sources & evidence

ORD record
ord-15bf92b4a5a1490ca6e652d5bc362d4c
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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