(Oxetan-3-yl)methanamine → 10-bromo-9-fluoro-N3-(oxetan-3-ylmethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2,3-dicarboxamide
Reaction equation
[Br:1][C:2]1[C:3]([F:22])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12]([C:18]([OH:20])=O)=[C:13]([C:15](=[O:17])[NH2:16])[N:14]=[C:7]3[C:6]=2[CH:21]=1.[O:23]1[CH2:26][CH:25]([CH2:27][NH2:28])[CH2:24]1>>[Br:1][C:2]1[C:3]([F:22])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[C:12]([C:18]([NH:28][CH2:27][CH:25]4[CH2:26][O:23][CH2:24]4)=[O:20])=[C:13]([C:15]([NH2:16])=[O:17])[N:14]=[C:7]3[C:6]=2[CH:21]=1Participants
Procedure
10-Bromo-2-carbamoyl-9-fluoro-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-3-carboxylic acid (55 mg) was reacted with oxetan-3-ylmethanamine similar to as described in Example 2 to produce crude 10-bromo-9-fluoro-N3-(oxetan-3-ylmethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2,3-dicarboxamide which was then reacted with 2-Methyl-3-butyne-ol similar to as described in Procedure E to afford 13 mg of 9-fluoro-10-(3-hydroxy-3-methyl-but-1-ynyl)-N3-(oxetan-3-ylmethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2,3-dicarboxamide following reverse phase hplc purification. MS (Q1) 443 (M)+. 1H NMR (400 MHz, DMSO) δ 11.37 (t, 1H), 8.61 (d, J=8.4 Hz, 1H), 8.39 (s, 1H), 7.89 (s, 1H), 7.01 (d, J=10.5 Hz, 1H), 5.48 (s, 1H), 5.05-4.93 (m, 2H), 4.68-4.61 (m, 2H), 4.58-4.50 (m, 2H), 4.35 (t, J=6.0 Hz, 2H), 3.56 (t, J=6.1 Hz, 2H), 3.21-3.13 (m, 1H), 1.49 (s, 6H).
Sources & evidence
- ORD record
- ord-755801d07cf04e96a234e8f104d95574
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09034866B2
Reaction notes
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