Cesium carbonate → 6-Chloro-1-methyl-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-1H-benzo[d]imidazol-4-amine

HRID 1024043Notes

Reaction equation

HRID 1024043 reaction equation
Br[C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH3:11])[C:6]=2[CH:5]=[C:4]([Cl:12])[CH:3]=1.[O:13]1[CH2:16][CH:15]([N:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:24]=[CH:25][C:26]([NH2:29])=[N:27][CH:28]=3)[CH2:19][CH2:18]2)[CH2:14]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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]>[Cl:12][C:4]1[CH:3]=[C:2]([NH:29][C:26]2[CH:25]=[CH:24][C:23]([N:20]3[CH2:21][CH2:22][N:17]([CH:15]4[CH2:14][O:13][CH2:16]4)[CH2:18][CH2:19]3)=[CH:28][N:27]=2)[C:10]2[N:9]=[CH:8][N:7]([CH3:11])[C:6]=2[CH:5]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866841255-[4-(3-Oxetanyl)-1-piperazinyl]-2-pyridinamineHCID 866841384-Bromo-6-chloro-1-methyl-1H-benzo[d]imidazole

Product 1

HCID 866841396-Chloro-1-methyl-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)-1H-benzo[d]imidazol-4-amineYield 108.1%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

A microwave vial equipped with a magnetic stirrer was charged with 109d (486 mg, 2.0 mmol), 5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-amine (390 mg 1.67 mmol), cesium carbonate (1.09 g, 3.34 mmol), tris(dibenzylideneacetone)dipalladium(0) (152 mg, 0.167 mmol) and Xantphos (193 mg, 0.334 mmol). After bubbling nitrogen through the suspension for 5 minutes, the reaction was heated at 120° C. for overnight. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was washed with a mixture of petroleum ether/ethyl acetate (15 mL, 2:1) to afford 109e as a yellow solid (720 mg, 100%). LCMS: [M+H]+ 399.3. 1H NMR (500 MHz, CDCl3) δ 8.20 (d, J=2.0, 1H), 8.04 (d, J=2.5, 1H), 7.72 (s, 1H), 7.61 (s, 1H), 7.28-7.29 (m, 1H), 6.90-6.91 (m, 2H), 4.70-4.71 (m, 4H), 3.77 (s, 3H), 3.70-3.71 (m, 1H), 3.17 (t, J=5.0, 4 H), 2.52 (t, J=5.0, 4H)

Workup

  1. customA microwave vial equipped with a magnetic stirrer
  2. customAfter bubbling nitrogen through the suspension for 5 minutes
  3. temperatureIt was then cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. washthe residue was washed with a mixture of petroleum ether/ethyl acetate (15 mL, 2:1)

Sources & evidence

ORD record
ord-f1e6d30d4c854d6fa58628d546849413
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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