1-(4-Fluorophenyl)pyrazole-4-boronic acid → [Bis-(4-methoxy-phenyl)-phenyl-methyl]-((4R,5R)-5-fluoro-4-{2-fluoro-5-[1-(4-fluoro-phenyl)-1H-pyrazol-4-yl]-phenyl}-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl)-amine

HRID 1626116Notes

Reaction equation

HRID 1626116 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[O:26][CH2:27][C@H:28]([F:40])[C@:29]([C:32]3[CH:37]=[C:36](Br)[CH:35]=[CH:34][C:33]=3[F:39])([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.[F:41][C:42]1[CH:47]=[CH:46][C:45]([N:48]2[CH:52]=[C:51](B(O)O)[CH:50]=[N:49]2)=[CH:44][CH:43]=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[O:26][CH2:27][C@H:28]([F:40])[C@:29]([C:32]3[CH:37]=[C:36]([C:51]4[CH:50]=[N:49][N:48]([C:45]5[CH:46]=[CH:47][C:42]([F:41])=[CH:43][CH:44]=5)[CH:52]=4)[CH:35]=[CH:34][C:33]=3[F:39])([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 467386841-(4-Fluorophenyl)pyrazole-4-boronic acidHCID 71008920[bis-(4-methoxy-phenyl)-phenyl-methyl]-[(4R,5R)-4-(5-bromo-2-fluoro-phenyl)-5-fluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-amine

Product 1

HCID 71008713[Bis-(4-methoxy-phenyl)-phenyl-methyl]-((4R,5R)-5-fluoro-4-{2-fluoro-5-[1-(4-fluoro-phenyl)-1H-pyrazol-4-yl]-phenyl}-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl)-amineYield 75%

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

In a manner analogous to that described in Example 9 a), the cross coupling reaction of [bis-(4-methoxy-phenyl)-phenyl-methyl]-[(4R,5R)-4-(5-bromo-2-fluoro-phenyl)-5-fluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-amine (intermediate C4.3) with 1-(4-fluorophenyl)-1H-pyrazol-4-ylboronic acid (CAS [1072945-89-1]) and tetrakis(triphenylphosphine)-palladium(0) as the catalyst yielded the title compound (75% yield) as a white foam. MS (ISP): m/z=689.3 [M+H]+.

Sources & evidence

ORD record
ord-7c39cf5e72b14d3bb245f5aa8c6adcb6
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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