N-methyl-2-pyrrolidone → HCID 117739052, compound

HRID 1506995Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:28])[N:5]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[C:6]([C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])=[N:7]2.[CH3:29][N:30]1C(=O)CCC1>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:29]([C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:28])[N:5]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[C:6]([C@@H:12]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH3:13])=[N:7]2)#[N:30]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (S)-tert-butyl 1-(5-bromo-4-oxo-3-(pyridin-3-yl)-3,4-dihydroquinazolin-2-yl)ethylcarbamate (255 mg, 0.58 mmol) in NMP (2 mL) was added zinc cyanide (74 mg, 0.63 mmol) and (PPh3)4Pd (66 mg, 0.06 mmol). The resulting suspension was degassed under Argon and heated to 80° C. for 5 hours. The reaction was poured into EtOAc, washed twice with aq. NaHCO3 and once with brine. Purification by flash chromatography (0-75% EtOAc/hexanes) provided (S)-tert-butyl 1-(5-cyano-4-oxo-3-(pyridin-3-yl)-3,4-dihydroquinazolin-2-yl)ethylcarbamate 196 mg (87%). ES/MS 392.1 (M+H+).

Workup

customThe resulting suspension was degassed under Argon
additionThe reaction was poured into EtOAc
washwashed twice with aq. NaHCO3 and once with brine
customPurification by flash chromatography (0-75% EtOAc/hexanes)

Sources & evidence

ORD record: ord-61453700ff39448d8394ff23ba73ab6d
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221795B2

Reaction notes

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