Potassium Carbonate → [3-(3-Butyl-4-oxo-3,4,4a,5,8,8a-hexahydro-phthalazin-1-yl)-2-methyl-indol-1-yl]-acetic acid

HRID 1453736Notes

Reaction equation

[CH2:1]([N:5]1[N:14]=[C:13]([C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][C:16]=2[CH3:24])[CH:12]2[CH:7]([CH2:8][CH:9]=[CH:10][CH2:11]2)[C:6]1=[O:25])[CH2:2][CH2:3][CH3:4].C([O-])([O-])=O.[K+].[K+].Br[CH2:33][C:34]([O:36]C(C)(C)C)=[O:35]>CN(C=O)C.CCOC(C)=O>[CH2:1]([N:5]1[C:6](=[O:25])[CH:7]2[CH:12]([CH2:11][CH:10]=[CH:9][CH2:8]2)[C:13]([C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]([CH2:33][C:34]([OH:36])=[O:35])[C:16]=2[CH3:24])=[N:14]1)[CH2:2][CH2:3][CH3:4]

Participants

Conditions

Temperature: 75 °C

Procedure

The product of step b) was dissolved in DMF (4 mL) and treated with K2CO3 (0.7 mmol, 97 mg) and t-butyl bromoacetate (0.5 mmol, 74 uL). After heating at 75° C. for 2 h, the reaction was cooled, diluted with EtOAc (10 mL) and washed 3× water. The organic solution was concentrated to dryness and treated with 4 mL TFA for 1.5 h. The reaction was concentrated and the title compound was purified by preparative LCMS. 1H NMR (DMSO-d6) δ 7.76 (d, J=8.1 Hz, 1H), 7.30 (d, J=7.5 Hz, 1H), 7.09-6.99 (m, 2H), 5.70 (d, J=10.8 Hz, 1H), 5.63 (d, J=10.8 Hz, 1H), 3.91 (dt, J=6.9, 13.2 Hz, 1H), 3.62 (dt, J=6.6, 13.2 Hz, 1H), 3.36 (quint., J=5.7 Hz, 1H), 2.96 (t, J=5.1 Hz, 1H), 2.79-2.71 (m, 1H), 2.35-1.94 (m, 4H), 1.64 (quint., J=7.1 Hz, 2H), 1.31 (sext., J=7.5 Hz, 1H), 0.91 (t, J=7.2 Hz, 3H); MS: ESI (negative): 392 (M−H).

Workup

temperaturethe reaction was cooled
washwashed 3× water
concentrationThe organic solution was concentrated to dryness
additiontreated with 4 mL TFA for 1.5 h
concentrationThe reaction was concentrated
customthe title compound was purified by preparative LCMS

Sources & evidence

ORD record: ord-5d668f4e50fc472f9de13554312de88e
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07476667B2

Reaction notes

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