Hydrochloric Acid → (+)-3-(5-cyanobenzo[d]oxazol-2-yl)-3-(5-methoxy-7-methyl-1H-indol-4-yl)propanoic acid

HRID 2174118Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH:11]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][N:21]4C(OC(C)(C)C)=O)[CH2:12][C:13]([O:15]C)=[O:14])=[N:8][C:7]=2[CH:36]=1)#[N:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CO.C(Cl)Cl>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH:11]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][NH:21]4)[CH2:12][C:13]([OH:15])=[O:14])=[N:8][C:7]=2[CH:36]=1)#[N:2]

Participants

Conditions

Temperature: 65 °C

Procedure

(±)-tert-Butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)-3-methoxy-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 148-A) (0.3 g, 0.613 mmol) was dissolved in MeOH (6 ml). cesium carbonate (0.998 g, 3.06 mmol) was added and the reaction was heated at 65° C. for 2.5 hours. The reaction was then cooled to room temperature and treated with 1 N HCl until pH=˜3. The mixture was then diluted with DCM and passed through a phase separator, concentrated and purified via preparative HPLC (HC-B) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.00 (br. s., 1H) 8.34 (t, J=1.14 Hz, 1H) 7.58-7.92 (m, 2H) 7.22 (t, J=2.78 Hz, 1H) 6.77 (s, 1H) 6.22 (dd, J=3.03, 1.89 Hz, 1H) 5.39 (dd, J=9.85, 4.67 Hz, 1H) 3.72 (s, 3H) 3.57 (dd, J=16.67, 9.98 Hz, 1H) 2.74 (dd, J=16.67, 4.67 Hz, 1H) 2.44 (d, J=0.63 Hz, 3H). HRMS calcd. for C21H17N3O4 (M+H)+ 376.1297. found 376.1290.

Workup

temperatureThe reaction was then cooled to room temperature
concentrationconcentrated
custompurified via preparative HPLC (HC-B)

Sources & evidence

ORD record: ord-4de25fed41fe4197a8a4eecefac5e2ef
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056874B2

Reaction notes

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