Potassium Carbonate → [3-(2-Methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-indol-1-yl]-acetic acid

HRID 1819582Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[N:11]2[CH3:20])=[CH:2]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:28][C:29]([O:31]C(C)(C)C)=[O:30]>CN(C=O)C.CCOC(C)=O>[CH3:20][N:11]1[C:12](=[O:19])[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]1[C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]([CH2:28][C:29]([OH:31])=[O:30])[CH:2]=1

Participants

Conditions

Temperature: 100 °C

Procedure

The product from example 20, step b) (450 mg, 1.72 mmol) was dissolved in DMF and treated with K2CO3 (284 mg, 2.06 mmol) followed by t-butyl bromoacetate (255 μL, 1.72 mmol). The reaction was heated to 100° C. for 5 h. The reaction was cooled, diluted with EtOAc, washed 3 times with water, and concentrated. The crude product was treated with TFA (neat) at room temperature for 45 minutes. The reaction was then concentrated to dryness and purified by preparative LCMS to give the title compound. 1H NMR (CD3OD) δ 7.74-7.78 (m, 1H), 7.43 (t, J=3.7 Hz, 1H), 7.41 (t, J=3.6 Hz, 1H), 7.36 (s, 1H), 7.28-7.31 (m, 1H), 7.20 (d, J=8.1 Hz, 1H), 6.96 (t, J=7.2 Hz, 1H), 6.67 (t, J=7.2 Hz, 1H), 6.48 (d, J=7.8 Hz, 1H), 4.62 (s, 2H), 2.78 (s, 3H); MS: ESI (negative): 319 (M−H).

Workup

temperatureThe reaction was cooled
washwashed 3 times with water
concentrationconcentrated
additionThe crude product was treated with TFA (neat) at room temperature for 45 minutes
concentrationThe reaction was then concentrated to dryness
custompurified by preparative LCMS

Sources & evidence

ORD record: ord-2224b89c497a40cd86e77ea63c984c5c
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07601749B2

Reaction notes

Loading…