Binap, (A+-)- → HCID 71255219, compound

HRID 540251Notes

Reaction equation

HRID 540251 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:25])(=[O:24])[CH2:15][CH2:14]2)[CH:3]=1.[NH2:26][C:27]1([CH2:31][NH:32][C:33](=[O:39])OC(C)(C)C)[CH2:30][O:29][CH2:28]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Na]>C1(C)C=CC=CC=1.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:24]=[S:16]1(=[O:25])[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[CH2:19][N:13]([C:4]2[CH:3]=[C:2]([N:26]3[C:33](=[O:39])[NH:32][CH2:31][C:27]43[CH2:30][O:29][CH2:28]4)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=3)[N:5]=2)[CH2:14][CH2:15]1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 5360545SodiumHCID 71254478tert-Butyl [(3-aminooxetan-3-yl)methyl]carbamateHCID 712545984-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

Product 1

HCID 71255219HCID 71255219, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (372 mg, 1.0 mmol, prepared in analogy to the one in Example 17-1), tert-butyl [(3-aminooxetan-3-yl)methyl]carbamate (202 mg, 1.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (91 mg, 0.10 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (62 mg, 0.10 mmol) and sodium tert-buoxide (192 mg, 2.0 mmol) in toluene (10 mL) was heated at 110° C. overnight. The resulting mixture was diluted with water (20 mL), and extracted with dichloromethane (20 mL×3). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC to afford 15 mg of the title compound. MS obsd. (ESI+) [(M+H)+] 465, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.15 (s, 1 H), 7.98-7.96 (d, J=7.2 Hz, 1 H), 7.90-7.87 (m, 1 H), 7.68-7.64 (m, 1 H), 7.53-7.46 (m, 2 H), 7.37-7.34 (m, 2 H), 7.17 (s, 1 H), 5.14 (s, 2 H), 4.80-4.74 (m, 4 H), 4.44 (s, 2 H), 4.27 (s, 2 H), 3.66-3.64 (t, J=4.8, 4.4 Hz, 2 H), 2.36 (s, 3 H).

Workup

  1. extractionextracted with dichloromethane (20 mL×3)
  2. washThe combined organic layers were washed with brine (50 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-0e1bc1366a2748a4910811b85329f04b
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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