Acetylethanolamine → N-(2-{[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]oxy}ethyl)acetamide

HRID 540271Notes

Reaction equation

HRID 540271 reaction equation
[OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:7])[CH3:6].Cl[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16](OC(F)(F)F)[CH:17]=2)[N:12]=[C:11]([N:24]2[CH2:30][C:29]3[CH:31]=[CH:32][CH:33]=[CH:34][C:28]=3[S:27](=[O:36])(=[O:35])[CH2:26][CH2:25]2)[CH:10]=1.[CH3:37]C(C)([O-])C.[Na+]>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[O:35]=[S:27]1(=[O:36])[C:28]2[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=2[CH2:30][N:24]([C:11]2[CH:10]=[C:9]([O:1][CH2:2][CH2:3][NH:4][C:5](=[O:7])[CH3:6])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH3:37])[CH:17]=3)[N:12]=2)[CH2:25][CH2:26]1

Participants

7

Reactant 3

HCID 8880AcetylethanolamineHCID 23676156Sodium t-butoxideHCID 712545694-(4-Chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

Product 1

HCID 71255227N-(2-{[2-(1,1-Dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]oxy}ethyl)acetamideYield 1.9%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of N-(2-hydroxyethyl)-acetamide (247 mg, 2.4 mmol), 4-(4-bromo-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (1000 mg, 2.4 mmol, prepared in analogy to 4-(4-chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 17-1), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride (190.4 mg, 0.24 mmol), 1,1′-bis(diphenylphosphino)ferrocene (129.3 mg, 0.24 mmol) and sodium tert-butoxide (460.8 mg, 4.8 mmol) in 1,4-dioxane (5 mL) was heated with stirring in a sealed 10 mL of microwave process vial for 1 hour at 130° C. under microwave irradiation. The reaction mixture was concentrated in vacuo and the residue was purified by preparative HPLC to afford 20 mg of the desired product (yield was 1.9%).

Workup

  1. temperaturewas heated
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-9db7333ad973463884b1f3952c808e9a
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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