Acetamide → N-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-yl]acetamide

HRID 1619248Notes

Reaction equation

HRID 1619248 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]([NH2:23])(=[O:22])[CH3:21].C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].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]([NH:23][C:20](=[O:22])[CH3:21])[CH:19]=[CH:18][C:5]=4[N:6]=3)[CH2:10][CH2:11]2)[CH2:17][CH2:16]1

Participants

8

Reactant 4

HCID 178AcetamideHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 595888036-Bromo-2-(4-cyclopropylpiperazin-1-yl)benzothiazole

Product 1

HCID 23728857N-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-yl]acetamideYield 24%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-bromo-2-(4-cyclopropylpiperazin-1-yl)benzothiazole (480 mg, 1.42 mmol), acetamide (251 mg, 4.26 mmol), Pd(OAc)2 (15.9 mg, 0.071 mmol), Cs2CO3 (694 mg, 2.13 mmol) and xantphos (62 mg, 0.107 mmol) in 1,4-dioxane (10 mL) was heated at reflux for 12 h. Water (5 mL) was added and the mixture was filtered. The filtrate was extracted with EtOAc (3×5 mL). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated to give a residue, which was purified by the preparative HPLC to give 108 mg (24%) of N-[2-(4-cyclopropylpiperazin-1-yl)benzothiazol-6-yl]acetamide as a trifluoroacetate salt.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 12 h
  3. filtrationthe mixture was filtered
  4. extractionThe filtrate was extracted with EtOAc (3×5 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customto give a residue, which
  9. customwas purified by the preparative HPLC

Sources & evidence

ORD record
ord-3351aa586f3a40cc8b5aa2c4f0d2a2eb
Source dataset
uspto-grants-2014_07
Patent number
US08772285B2

Reaction notes

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