2-Bromopyridine → HCID 59837383, compound

HRID 273073Notes

Reaction equation

HRID 273073 reaction equation
[O:1]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3([CH2:24][NH2:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:14][CH:13]=2)[CH2:3][CH2:2]1.Br[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH3:4].[O:1]1[CH2:7][CH2:6][CH2:5][N:4]([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3([CH2:24][NH:25][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:14][CH:13]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 79732-BromopyridineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 68576757HCID 68576757, compound

Product 2

HCID 222AmmoniaHCID 59837383HCID 59837383, compoundYield 117.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

C-{4-[4-(3-[1,4]Oxazepan-4-yl-propoxy)-phenyl]-tetrahydro-pyran-4-yl}-methylamine (210 mg, 0.48 mmol) was added to a solution of 2-bromopyridine (70 mg, 0.42 mmol), Pd2(dba)3 (91 mg, 0.1 mmol), BINAP (126 mg, 2 mmol) and sodium tert-butoxide (56 mg, 5.7 mmol) in toluene (3 ml). This solution was heated in the microwave (Smith Personal Synthesiser) at 110° C. for 15 minutes. The solution was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by column chromatography, eluting with a gradient of DCM:MeOH:NH3 (from 99:1:0.1 to 95:5:0.5) to afford the title compound as a yellow oil (120 mg, 59%). 1H NMR (400 MHz, CD3OD) δ 1.88-2.00 (m, 6H), 2.17 (m, 2H), 2.68-2.79 (m, 6H), 3.43 (s, 2H), 3.50 (m, 2H), 3.76 (m, 2H), 3.80 (m, 4H), 4.03 (t, 2H), 6.39 (d, 1H), 6.44 (t, 1H), 6.91 (d, 2H), 7.33 (m, 3H), 7.81 (d, 1H). HRMS ESI+ m/z 426.2741 [MH]+.

Workup

  1. filtrationThe solution was filtered through Celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was purified by column chromatography
  4. washeluting with a gradient of DCM

Sources & evidence

ORD record
ord-d0965c37cb33455889a4925c8e39514c
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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