Ethanol → 6-(5-(Methylthio)-1,3,4-thiadiazol-2-yl)benzo[d]isothiazole

HRID 2075383Notes

Reaction equation

Br[C:2]1[S:3][C:4]([S:7][CH3:8])=[N:5][N:6]=1.CC1(C)C(C)(C)OB([C:17]2[CH:18]=[CH:19][C:20]3[S:24][N:23]=[CH:22][C:21]=3[CH:25]=2)O1.C([O-])([O-])=O.[Na+].[Na+].CCO>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.COCCOC.O>[CH3:8][S:7][C:4]1[S:3][C:2]([C:18]2[CH:17]=[CH:25][C:21]3[CH:22]=[N:23][S:24][C:20]=3[CH:19]=2)=[N:6][N:5]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a stirred mixture of 2-bromo-5-(methylthio)-1,3,4-thiadiazole (0.22 g, 1.0 mmol) (prepared as described in WO 97/30981), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]isothiazole (0.18 g 0.69 mmol), Na2CO3 (0.22 g, 2.1 mmol), and Pd(PPh3)4 (80 mg, 0.07 mmol) was added EtOH (1.0 mL), water (1.0 mL) and DME (3.0 mL). The resulting mixture was heated at 90° C. overnight and at 140° C. for 30 minutes. The mixture was cooled and passed through a short path of Celite, washing with DCM (3×10 mL). The combined organic phases were concentrated to give the crude residue. Purification by chromatography on silica gel (DCM—5% MeOH in DCM) gave the product as an off-white powder (0.16 g, 87%). LCMS (API-ES) m/z (%): 266.4 (100%, M+H+); 1H NMR (400 MHz, CDCl3): δ ppm 8.97 (s, 1 H) 8.48 (s, 1 H) 8.16 (d, J=8.53 Hz, 1 H) 8.00 (d, J=8.03 Hz, 1 H) 2.87 (s, 3 H).

Workup

temperatureThe mixture was cooled
washwashing with DCM (3×10 mL)
concentrationThe combined organic phases were concentrated
customto give the crude residue
customPurification by chromatography on silica gel (DCM—5% MeOH in DCM)

Sources & evidence

ORD record: ord-99f3873f5ef24015bc3a29c6bb93eb2f
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07919504B2

Reaction notes

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