Hydrochloric Acid → (R)-(1-amino-but-3-ynyl)-7-chloro-3-phenylamino-3H-quinazolin-4-one

HRID 1517348Notes

Reaction equation

HRID 1517348 reaction equation
C(OC(=O)[NH:7][C@@H:8]([C:12]1[N:21]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20](=[O:29])[C:19]2[C:14](=[CH:15][C:16]([Cl:30])=[CH:17][CH:18]=2)[N:13]=1)[CH2:9][C:10]#[CH:11])(C)(C)C.Cl>CO.O1CCOCC1>[NH2:7][C@@H:8]([C:12]1[N:21]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20](=[O:29])[C:19]2[C:14](=[CH:15][C:16]([Cl:30])=[CH:17][CH:18]=2)[N:13]=1)[CH2:9][C:10]#[CH:11]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57695453(R)-[1-(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3-ynyl]-carbamic acid tert-butyl ester

Product 1

HCID 57516539(R)-(1-amino-but-3-ynyl)-7-chloro-3-phenylamino-3H-quinazolin-4-oneYield 111.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of (R)-[1-(7-chloro-4-oxo-3-phenylamino-3,4-dihydro-quinazolin-2-yl)-but-3-ynyl]-carbamic acid tert-butyl ester (5.35 g, 12.2 mmol) in methanol (65 ml) was added HCl in dioxane (4M, 20 ml). The resulting solution was stirred and the reaction completion was monitored using HPLC/LCMS. The solvent was then removed and the mixture was triturated with diethyl ether to afford 2-((R)-1-amino-but-3-ynyl)-7-chloro-3-phenylamino-3H-quinazolin-4-one (4.60 g, 100%) as off-white solid. M.p. 175-180° C. LCMS: m/e 339 [M+H]. 1H NMR: (DMSO d6) δ 9.27 (s, 1H), 8.73 (s, br, 3H), 8.15 (d, J=8.4 Hz, 1H), 7.79 (d, J=2.0 Hz, 1H), 7.70 (dd, J=2.0 and 8.4 Hz, 1H), 7.32 (t, J=8.0 Hz, 2H), 6.92 (t, J=7.6 Hz 1H), 6.68 (m, 2H), 4.90, 4.58 (m, 1H, rotomers), 3.18 (m, 1H), 3.08 (m 2H).

Workup

  1. customThe solvent was then removed
  2. customthe mixture was triturated with diethyl ether

Sources & evidence

ORD record
ord-882995782067413b8c04ab93b3be46cc
Source dataset
uspto-grants-2012_07
Patent number
US08232285B2

Reaction notes

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