Cesium carbonate → 1-((1H-indol-4-yl)methyl)-9-(benzo[d]oxazol-2-yl)-1,9-diazaspiro[5.5]undecan-2-one

HRID 41566Notes

Reaction equation

HRID 41566 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[O:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[N:16]1[CH2:47][CH2:46][C:19]2([N:24]([CH2:25][C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[CH:28]=[CH:29][N:30]4S(C3C=CC(C)=CC=3)(=O)=O)[C:23](=[O:45])[CH2:22][CH2:21][CH2:20]2)[CH2:18][CH2:17]1>CO>[NH:30]1[C:31]2[C:27](=[C:26]([CH2:25][N:24]3[C:19]4([CH2:18][CH2:17][N:16]([C:8]5[O:7][C:11]6[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=6[N:9]=5)[CH2:47][CH2:46]4)[CH2:20][CH2:21][CH2:22][C:23]3=[O:45])[CH:34]=[CH:33][CH:32]=2)[CH:28]=[CH:29]1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 672523209-(benzo[d]oxazol-2-yl)-1-((1-tosyl-1H-indol-4-yl)methyl)-1,9-diazaspiro[5.5]undecan-2-one

Product 1

HCID 532596351-((1H-indol-4-yl)methyl)-9-(benzo[d]oxazol-2-yl)-1,9-diazaspiro[5.5]undecan-2-oneYield 69.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Cs2CO3 (430 mg, 1.32 mmol) was added to a stirred solution of 9-(benzo[d]oxazol-2-yl)-1-((1-tosyl-1H-indol-4-yl)methyl)-1,9-diazaspiro[5.5]undecan-2-one (250 mg, 0.44 mmol) in methanol (10 mL) and stirring was continued for 18 h at 78° C. The reaction mixture was concentrated, water was added to the residue and extracted with ethyl acetate (2×50 mL), dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by reversed phase HPLC (column Zorbax eclipseXDB C18 21.2×150 mm 5 ♀m, flow 20 mL/min, eluent: gradient water/acetonitrile) to yield the title compound (126 mg, 69%). [1H NMR (400 MHz, CDCl3) ♀ ppm 8.30 (br s, 1H), 7.36-6.96 (m, 7H), 6.78 (d, 1H), 6.46 (m, 1H), 4.95 (s, 2H), 4.16 (dd, 2H), 3.18 (t, 2H), 2.65 (t, 2H), 2.20-2.05 (m, 4H), 1.95-1.88 (m, 2H), 1.75-1.61 (m, 2H); LCMS RtE=1.32 min, [M+H]+=415.1].

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionwater was added to the residue
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by reversed phase HPLC (column Zorbax eclipseXDB C18 21.2×150 mm 5 ♀m, flow 20 mL/min, eluent: gradient water/acetonitrile)

Sources & evidence

ORD record
ord-e7ddcf3b1c1745f3adcdb280eccd2bef
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Reaction notes

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