Cesium carbonate → (+/-)-4-(5-cyanobenzo[d]oxazol-2-yl)-4-(5-methoxy-7-methyl-1H-indol-4-yl)pentanoic acid

HRID 2174124Notes

Reaction equation

HRID 2174124 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([C:19]3[C:27]([O:28][CH3:29])=[CH:26][C:25]([CH3:30])=[C:24]4[C:20]=3[CH:21]=[CH:22][N:23]4C(OC(C)(C)C)=O)([CH2:13][CH2:14][C:15]([O:17]C)=[O:16])[CH3:12])=[N:8][C:7]=2[CH:38]=1)#[N:2].C(=O)([O-])[O-].[Cs+].[Cs+]>CO>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([C:19]3[C:27]([O:28][CH3:29])=[CH:26][C:25]([CH3:30])=[C:24]4[C:20]=3[CH:21]=[CH:22][NH:23]4)([CH3:12])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])=[N:8][C:7]=2[CH:38]=1)#[N:2]

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 86701765(+/-)-tert-Butyl 4-(2-(5-cyanobenzo[d]oxazol-2-yl)-5-methoxy-5-oxopentan-2-yl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701766(+/-)-4-(5-cyanobenzo[d]oxazol-2-yl)-4-(5-methoxy-7-methyl-1H-indol-4-yl)pentanoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (±)-tert-Butyl 4-(2-(5-cyanobenzo[d]oxazol-2-yl)-5-methoxy-5-oxopentan-2-yl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 150-B) (83 mg, 0.160 mmol) and cesium carbonate (261 mg, 0.802 mmol) in MeOH (1.6 mL) was heated to 60° C. and stirred for 2 hrs. The reaction was cooled down to rt and quenched with a saturated solution of ammonium chloride, MeOH was then removed in vacuo. The residue was diluted with AcOEt and water. The layers were separated and the water layer was extracted with AcOEt. The combined organic layers were passed through a phase separator and purified by preparative HPLC (HC-B) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.05 (br. s., 1H) 8.32 (d, J=1.26 Hz, 1H) 7.66-7.89 (m, 2H) 7.30 (t, J=2.91 Hz, 1H) 6.69 (s, 1H) 6.38 (dd, J=3.03, 1.77 Hz, 1H) 3.51 (s, 3H) 2.58-2.65 (m, 2H) 2.44 (s, 3H) 2.15 (dd, J=9.73, 6.69 Hz, 2H) 1.91 (s, 3H). HRMS calcd. for C23H21N3O4 (M+H)+ 404.1610. found 404.1607.

Workup

  1. temperatureThe reaction was cooled down to rt
  2. customquenched with a saturated solution of ammonium chloride, MeOH
  3. customwas then removed in vacuo
  4. additionThe residue was diluted with AcOEt and water
  5. customThe layers were separated
  6. extractionthe water layer was extracted with AcOEt
  7. custompurified by preparative HPLC (HC-B)

Sources & evidence

ORD record
ord-f9e0588fcf384bff8097d48e97c2342f
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

Loading…