Methanesulfonic Acid → HCID 18932824, compound

HRID 1597966Notes

Reaction equation

[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[C:11]2[C:20]3[C:15](=[CH:16][C:17]([OH:23])=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][N:12]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OCC)=O)=O)C.O[CH2:56][CH2:57][N:58]1[CH2:63][CH2:62][O:61][CH2:60][CH2:59]1.[CH3:64][S:65]([OH:68])(=[O:67])=[O:66]>C1COCC1.C(Cl)Cl>[CH3:64][S:65]([OH:68])(=[O:67])=[O:66].[CH3:64][S:65]([OH:68])(=[O:67])=[O:66].[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:23][CH2:56][CH2:57][N:58]4[CH2:63][CH2:62][O:61][CH2:60][CH2:59]4)=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][N:12]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 20 °C

Procedure

To a stirred solution of 4-(6-chloro-2,3-dihydro-indol-1-yl)-6-methoxy-quinazolin-7-ol (200 mg, 0.610 mmol; from Example 70) and triphenylphosphine(160 mg, 0.610 mmol) in dry THF (3 mL) under N2(g) was added diethyl-azodicarboxylate (106 μL, 0.671 mmol) dropwise at 0° C. over 10 minutes followed by a solution of 4-(2-hydroxyethyl)-morpholine (81 μL, 0.671 mmol) in dry THF (0.8 mL). The mixture was allowed to warm to 20° C. and stirred 16 hours before quenching with H2O (20μL) and concentrating in vacuo. Flash chromatography of the residue on silica using first 45% acetone/CH2Cl2 followed by 10% MeOH/CH2Cl2 eluted the product as its free-base (180 mg), which was precipitated as its bis(methanesulfonate) salt by addition of 2.0 eq. of methanesulfonic acid to a solution in CH2Cl2. (M.P. 150°-158° C. (dec); LC-MS: 441 (MH+); anal. RP18-HPLC RT: 3.76 min.).

Workup

custombefore quenching with H2O (20μL)
concentrationconcentrating in vacuo
washeluted the product as its free-base (180 mg), which

Sources & evidence

ORD record: ord-78b22ccb58c345d08bb99afece2baa1d
Source dataset: uspto-grants-1998_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05736534

Reaction notes

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