Water → HCID 86691416, compound

HRID 540233Notes

Reaction equation

HRID 540233 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](OC(F)(F)F)[CH:10]=2)[N:5]=[C:4]([N:17]2[CH2:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[S:20](=[O:29])(=[O:28])[CH2:19][CH2:18]2)[CH:3]=1.[NH2:30][C:31]1([CH2:35][NH:36][C:37](=[O:42])[C:38]([F:41])([F:40])[F:39])[CH2:34][O:33][CH2:32]1.[CH3:43]C(C)([O-])C.[Na+].O>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:28]=[S:20]1(=[O:29])[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[CH2:23][N:17]([C:4]2[CH:3]=[C:2]([NH:30][C:31]3([CH2:35][NH:36][C:37](=[O:42])[C:38]([F:39])([F:40])[F:41])[CH2:34][O:33][CH2:32]3)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:43])[CH:10]=3)[N:5]=2)[CH2:18][CH2:19]1

Participants

8

Reactant 4

HCID 962WaterHCID 23676156Sodium t-butoxideHCID 712545694-(4-Chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxideHCID 86691370HCID 86691370, compound

Product 1

HCID 86691416HCID 86691416, compoundYield 26.5%

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
120 °C

Procedure

A solution of 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (500 mg, 1.341 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), N-[(3-aminooxetan-3-yl)methyl]-2,2,2-trifluoroacetamide (570 mg, 70%, 2.01 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride (99 mg, 0.134 mmol), 1,1′-bis(diphenylphosphino)ferrocene (75 mg, 0.134 mmol), and sodium tert-butoxide (258 mg, 2.682 mmol) in 1,4-dioxane (8 mL) was heated with stirring in a sealed 10 mL of microwave process vial for 1.5 hours at 120° C. under microwave irradiation. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography (eluting with 1-10% methanol in dichloromethane) to afford 190 mg of the desired product (yield was 26%). MS obsd. (ESI+) [(M+H)+] 535, 1H NMR (400 MHz, CD3OD) δ ppm 7.98 (m, 1 H), 7.82 (d, J=6.8 Hz, 1 H), 7.66 (s, 1 H), 7.59 (td, J=0.8, 7.6 Hz, 1 H), 7.47-7.42 (m, 2 H), 7.32 (dd, J=1.6, 8.8 Hz, 1 H), 5.70 (s, 1 H), 5.18 (s, 2 H), 4.86 (m, 4 H), 4.52 (s, 2 H), 3.87 (s, 2 H), 3.60 (t, J=4.8 Hz, 2 H), 2.43 (s, 3 H).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash column chromatography (eluting with 1-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-519be7df192947a6907b94c4adbfeeef
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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