Phenylhydrazine → (R)-[1-(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3-ynyl]-carbamic acid tert-butyl ester

HRID 1517347Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][C:14]#[CH:15])[C:10](O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:16][C:17]1[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:18]=1[C:19]([OH:21])=O.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1.[C:49]1([NH:55][NH2:56])[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>N1C=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([C:10]1[N:56]([NH:55][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:19](=[O:21])[C:18]2[C:17](=[CH:25][C:24]([Cl:26])=[CH:23][CH:22]=2)[N:16]=1)[CH2:13][C:14]#[CH:15])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 55 °C

Procedure

To a mixture of (R)-2-tert-butoxycarbonylamino-pent-4-ynoic acid (5.0 g, 23.5 mmol) in anhydrous pyridine (20 ml) were added 2-amino-4-chloro-benzoic acid (4.03 g, 23.5 mmol) and triphenyl phosphite (7.40 ml). The reaction mixture was then heated at 55° C. for 16 h. To this was added phenylhydrazine (2.8 ml, 28.2 mmol). The resulting mixture was stirred at 100° C. for 8 h. After the solvent was removed, the residue was purified by flash column (hexane to 20% ethyl acetate in hexane) to give [(R)-1-(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3-ynyl]-carbamic acid tert-butyl ester (5.5 g, 53.4%) as off-white solid. M.p. 155-157° C. [LCMS]: 439 [M+H]. 400 MHz 1H NMR: (DMSO-d6) δ 9.21 and 9.0 (s, s, 1H, rotomers), 8.08 (m, 1H), 7.81 (m, 1H), 7.60 (dd, J=2.0, 6.4 Hz, 1H), 7.31-7.18 (m, 3H), 6.89-6.67 (m, 3H), 5.14-4.97 (m, br, 1H), 2.86 (m, br, 2H), 2.25 (m, 1H), 1.32 (s, 9H).

Workup

customAfter the solvent was removed
customthe residue was purified by flash column (hexane to 20% ethyl acetate in hexane)

Sources & evidence

ORD record: ord-63485482d3c0402d97f1bca042358390
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08232285B2

Reaction notes

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