2-Methylbut-3-yne-1,2-diol → (+/-) 9-(3,4-dihydroxy-3-methylbut-1-yn-1-yl)-10-fluoro-3-N-methyl-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-3,4-dicarboxamide

HRID 575129Notes

Reaction equation

HRID 575129 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[F:16])[CH:12]1[CH2:17][CH:10]([CH2:11]1)[N:9]1[C:5]2=[N:6][C:7]([C:18]([NH2:20])=[O:19])=[CH:8]1.Br[C:22]1[CH:23]=[C:24]2[C:33](=[CH:34][C:35]=1[F:36])[CH:32]1[CH2:37][CH:30]([CH2:31]1)[N:29]1[C:25]2=[N:26][C:27]([C:42]([NH2:44])=[O:43])=[C:28]1[C:38]([NH:40][CH3:41])=[O:39].[CH3:45][C:46]([OH:51])([C:49]#[CH:50])[CH2:47][OH:48]>>[OH:51][C:46]([CH3:45])([CH2:47][OH:48])[C:49]#[C:50][C:22]1[CH:23]=[C:24]2[C:33](=[CH:34][C:35]=1[F:36])[CH:32]1[CH2:37][CH:30]([CH2:31]1)[N:29]1[C:25]2=[N:26][C:27]([C:42]([NH2:44])=[O:43])=[C:28]1[C:38]([NH:40][CH3:41])=[O:39].[OH:51][C:46]([CH3:45])([CH2:47][OH:48])[C:49]#[C:50][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[F:16])[CH:12]1[CH2:17][CH:10]([CH2:11]1)[N:9]1[C:5]2=[N:6][C:7]([C:18]([NH2:20])=[O:19])=[CH:8]1

Participants

5

Reactant 3

HCID 221369052-Methylbut-3-yne-1,2-diolHCID 8669308010-bromo-9-fluoro-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamideHCID 866931549-bromo-10-fluoro-3-N-methyl-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-3,4-dicarboxamide

Product 2

HCID 71715395(+/-) 9-(3,4-dihydroxy-3-methylbut-1-yn-1-yl)-10-fluoro-3-N-methyl-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-3,4-dicarboxamideHCID 71715397(+/-) 9-(3,4-Dihydroxy-3-methylbut-1-yn-1-yl)-10-fluoro-2,5 diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-4-carboxamide

Procedure

A mixture of 9-bromo-10-fluoro-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-4-carboxamide and 9-bromo-10-fluoro-3-N-methyl-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-3,4-dicarboxamide (125 mg) was reacted with 2-methylbut-3-yne-1,2-diol similar to as described in Procedure E to afford 25.2 mg of (±) 9-(3,4-dihydroxy-3-methylbut-1-yn-1-yl)-10-fluoro-3-N-methyl-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-3,4-dicarboxamide [MS (Q1) 413 (M)+, 1H NMR (400 MHz, DMSO) δ 10.56 (q, J=4.6 Hz, 1H), 8.83 (d, J=7.5 Hz, 1H), 8.24 (s, 1H), 7.75 (s, 1H), 7.29 (d, J=10.0 Hz, 1H), 6.16-6.02 (m, 1H), 5.43 (s, 1H), 4.99 (t, J=6.1 Hz, 1H), 3.74-3.60 (m, 1H), 3.54-3.37 (m, 2H), 3.20-3.02 (m, 2H), 2.78 (d, J=4.5 Hz, 3H), 1.76-1.62 (m, 2H), 1.44 (s, 3H)] and 14.3 mg of (±) 9-(3,4-dihydroxy-3-methylbut-1-yn-1-yl)-10-fluoro-2,5 diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-4-carboxamide [MS (Q1) 356 (M)+. 1H NMR (400 MHz, DMSO) δ 8.65 (d, J=7.6 Hz, 1H), 7.82 (s, 1H), 7.51 (s, 1H), 7.27 (d, J=10.2 Hz, 1H), 7.09 (s, 1H), 5.45 (s, 1H), 5.01 (s, 1H), 4.91 (q, J=10.6, 1H), 3.75-3.67 (m, 1H), 3.44 (q, J=10.6 Hz, 2H), 3.14-3.03 (m, 2H), 1.68 (d, J=12.2 Hz, 2H), 1.43 (s, 3H).] following reverse phase hplc purification.

Sources & evidence

ORD record
ord-a6d8f855cb1e4aef82ecc175c7aab0af
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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