Diisopropylethylamine → 5-(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-3-nitropyridin-2-amine

HRID 241192Notes

Reaction equation

HRID 241192 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24](B5OC(C)(C)C(C)(C)O5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1.C(=O)([O-])O.[K+].[NH2:41][C:42]1[C:47]([N+:48]([O-:50])=[O:49])=[CH:46][C:45](Br)=[CH:44][N:43]=1.CCN(C(C)C)C(C)C>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:45]5[CH:46]=[C:47]([N+:48]([O-:50])=[O:49])[C:42]([NH2:41])=[N:43][CH:44]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 1388782-Amino-5-bromo-3-nitropyridineHCID 516893Potassium BicarbonateHCID 668205164-(5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine

Product 1

HCID 668206145-(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-3-nitropyridin-2-amineYield 37.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (1.3 g, 2.7 mmol), potassium hydrogen carbonate (1.4 g, 14 mmol), 2-amino-5-bromo-3-nitropyridine (0.98 g, 4.5 mmol) and DIPEA (1.4 mL, 8.2 mmol) in dioxane (8 mL) and water (1 mL) was added dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (0.20 g, 0.27 mmol). The biphasic mixture was then heated (90° C.) for 2 h and the organic layer was separated and purified by column chromatography on silica (0-10% methanol/dichloromethane) to provide 5-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-3-nitropyridin-2-amine (0.49 g, 37% yield) as a orange-red solid. MS (EI) for C26H23FN6O3: 487 (MH+).

Workup

  1. customthe organic layer was separated
  2. custompurified by column chromatography on silica (0-10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-52170f534d3743928dfa15c7e9689481
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

Loading…