(E)-N-(4-(3-bromophenylamino)quinazolin-6-yl)-4-morpholinobut-2-enamide → 4-((2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-4-oxo-2-butenyl)-4-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]morpholin-4-ium formate

HRID 1520732Notes

Reaction equation

HRID 1520732 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH:19][C:20](=[O:30])/[CH:21]=[CH:22]/[CH2:23][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.BrC[C:33]1[N:34]([CH3:41])[CH:35]=[C:36]([N+:38]([O-:40])=[O:39])[N:37]=1.[CH3:42]O.[CH:44]([OH:46])=[O:45].O>CN1C(=O)CCC1>[CH:44]([O-:46])=[O:45].[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[NH:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([NH:19][C:20](=[O:30])/[CH:21]=[CH:22]/[CH2:23][N+:24]3([CH2:42][C:35]4[N:34]([CH3:41])[CH:33]=[N:37][C:36]=4[N+:38]([O-:40])=[O:39])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:17]=2)[N:12]=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 5328973(E)-N-(4-(3-bromophenylamino)quinazolin-6-yl)-4-morpholinobut-2-enamideHCID 668237632-(bromomethyl)-1-methyl-4-nitro-1H-imidazoleHCID 86663602MeOH formic acid water

Product 1

HCID 469376184-((2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-4-oxo-2-butenyl)-4-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]morpholin-4-ium formateYield 12%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Reaction of (E)-N-(4-(3-bromophenylamino)quinazolin-6-yl)-4-morpholinobut-2-enamide (13) (1.0 g, 2.14 mmol) in NMP (4 mL) with 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole (105) (313 mg, 1.42 mmol) for 3.5 days according to general procedure D, followed by preparative HPLC using MeOH/formic acid/water as mobile phase gave 4-((2E)-4-{[4-(3-bromoanilino)-6-quinazolinyl]amino}-4-oxo-2-butenyl)-4-[(1-methyl-4-nitro-1H-imidazol-5-yl)methyl]morpholin-4-ium formate (24) (110 mg, 12%), m.p. 125-129° C. 1H NMR [(CD3)2SO] δ 11.69 (s, 1H), 10.17 (s, 1H), 9.28 (s, 1H), 8.65 (br, 1H), 8.61 (s, 1H), 8.44-8.40 (m, 2H), 8.14 (s, 1H), 8.07 (d, J=8.1 Hz, 1H), 7.34 (t, J=8.1 Hz, 1H), 7.27 (d, J=8.5 Hz, 1H), 7.17-7.10 (m, 2H), 6.82 (d, J=14.6 Hz, 1H), 5.12 (br s, 2H), 4.81 (br s, 2H), 4.16 (t, J=12.0 Hz, 2H), 3.91 (m, 2H), 3.88 (s, 3H), 3.70-3.60 (m, 2H), 3.46 (t, J=12.0 Hz, 2H). FIRMS (FAB+) found: 607.14189, 609.14034 (M-HCOO), calcd. for C27H2879/81BrN8O4+: 607.14169, 609.13964.

Sources & evidence

ORD record
ord-1992af659a9947838d041838f1f8cfad
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

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