Tetrahydrofuran → N-{4-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-yl]phenyl}-acetamide

HRID 1944678Notes

Reaction equation

Br[C:2]1[CH:19]=[CH:18][C:5]2[N:6]=[C:7]([N:9]3[CH2:14][CH2:13][N:12]([CH:15]4[CH2:17][CH2:16]4)[CH2:11][CH2:10]3)[S:8][C:4]=2[CH:3]=1.[C:20]([NH:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)(=[O:22])[CH3:21].C1COCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH:15]1([N:12]2[CH2:13][CH2:14][N:9]([C:7]3[S:8][C:4]4[CH:3]=[C:2]([C:27]5[CH:28]=[CH:29][C:24]([NH:23][C:20](=[O:22])[CH3:21])=[CH:25][CH:26]=5)[CH:19]=[CH:18][C:5]=4[N:6]=3)[CH2:10][CH2:11]2)[CH2:17][CH2:16]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 6-bromo-2-(4-cyclopropylpiperazin-1-yl)benzothiazole (500 mg, 1.48 mmol) and 4-acetamidophenylboronic acid (319 mg, 1.78 mmol) in a 5:1 mixture of THF and H2O (20 mL) was added Pd2(dba)3 (240 mg, 0.148 mmol), followed by P(t-Bu)3BF4 (86 mg, 0.296 mmol) and K3PO4.H2O (1.97 g, 7.4 mmol). The mixture was heated at 60° C. for 3 h, filtered and the volatiles were evaporated. Water (5 mL) was added and the mixture was extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by the preparative HPLC to give 42 mg (7%) of N-{4-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-yl]phenyl}-acetamide as a trifluoroacetate salt.

Workup

filtrationfiltered
customthe volatiles were evaporated
additionWater (5 mL) was added
extractionthe mixture was extracted with CH2Cl2 (3×20 mL)
dry with materialThe combined organic extracts were dried (Na2SO4)
concentrationconcentrated
customThe residue was purified by the preparative HPLC

Sources & evidence

ORD record: ord-142d59064fc14a81ba03e78bf406b037
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08394842B2

Reaction notes

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