Cesium carbonate → 3-(1-Hydroxyethyl)-4-(thiazol-5-yl)-1H-isochromen-1-one

HRID 634359Notes

Reaction equation

HRID 634359 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[O:4][C:3]=1[CH:13]([OH:15])[CH3:14].CN1CC(=O)OB([C:26]2[S:30][CH:29]=[N:28][CH:27]=2)OC(=O)C1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.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>[OH:15][CH:13]([C:3]1[O:4][C:5](=[O:12])[C:6]2[C:11]([C:2]=1[C:26]1[S:30][CH:29]=[N:28][CH:27]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH3:14]

Participants

6

Reactant 3

HCID 10796Cesium carbonate2×HCID 713099495-Thiazole boronic acid MIDA ester2×HCID 1181312554-Bromo-3-(1-hydroxyethyl)-1H-isochromen-1-one2×

Product 1

HCID 1181311813-(1-Hydroxyethyl)-4-(thiazol-5-yl)-1H-isochromen-1-oneYield 100.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 6228DimethylformamideSolvent

Procedure

4-Bromo-3-(1-hydroxyethyl)-1H-isochromen-1-one (Intermediate A2, 0.1 g, 0.372 mmol), 6-methyl-2-(thiazol-5-yl)-1,3,6,2-dioxazaborocane-4,8-dione (0.134 g, 0.56 mmol), Pd(PPh3)4 (0.021 g, 0.019 mmol) and Cs2CO3 (0.182 g, 0.56 mmol) in DMF (1 mL) were heated under microwave irradiation at 120° C. for 1 hrs and 15 min. Then, further 6-methyl-2-(thiazol-5-yl)-1,3,6,2-dioxazaborocane-4,8-dione (0.134 g, 0.56 mmol), Pd(PPh3)4 (0.021 g, 0.019 mmol) and Cs2CO3 (0.182 g, 0.56 mmol) were added and then resulting mixture was reacted for 5 hrs at 100° C. The crude product was purified via reverse phase chromatography with a Biotage C18 30 g SNAP column (Phase A, water 95%, ACN 4.9%, formic acid 0.1%; Phase B ACN 99.9%, formic acid 0.1%) to give the title compound (102 mg).

Workup

  1. customresulting mixture
  2. customwas reacted for 5 hrs at 100° C
  3. customThe crude product was purified via reverse phase chromatography with a Biotage C18 30 g SNAP column (Phase A, water 95%, ACN 4.9%, formic acid 0.1%; Phase B ACN 99.9%, formic acid 0.1%)

Sources & evidence

ORD record
ord-27c10fcd2fef4f88a6243542741877d5
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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