Dichloromethane → HCID 86268899, compound

HRID 1848745Notes

Reaction equation

HRID 1848745 reaction equation
Br[C:2]1[CH:35]=[CH:34][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[C:13]([O:16][CH2:17][C:18]4[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=4)[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]2[C:31]([OH:33])=[O:32])=[CH:4][CH:3]=1.C(Cl)Cl.[CH3:39][O:40][C:41]1[N:46]=[CH:45][C:44](B(O)O)=[CH:43][N:42]=1.C([O-])([O-])=O.[Na+].[Na+]>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].O1CCOCC1>[CH3:39][O:40][C:41]1[N:46]=[CH:45][C:44]([C:2]2[CH:3]=[CH:4][C:5]([CH2:6][N:7]3[C:11]4[CH:12]=[C:13]([O:16][CH2:17][C:18]5[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=5)[CH:14]=[CH:15][C:10]=4[N:9]=[C:8]3[C@H:25]3[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]3[C:31]([OH:33])=[O:32])=[CH:34][CH:35]=2)=[CH:43][N:42]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27367782-Methoxypyrimidine-5-boronic acidHCID 86268284HCID 86268284, compound

Product 1

HCID 86268899HCID 86268899, compoundYield 82.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a 5 mL vial were added racemic cis-2-(1-(4-bromobenzyl)-6-((5-methylpyridin-2-yl)methoxy)-1H-benzo[d]imidazol-2-yl)cyclohexanecarboxylic acid (77.2 mg, 0.14 mmol), Pd(dppf)Cl2.DCM (14 mg, 0.017 mmol), (2-methoxypyrimidin-5-yl)boronic acid (73 mg, 0.47 mmol), Na2CO3 (0.3 mL, 2M) and 1,4-dioxane (2 mL). The vial was flushed with N2 then capped and placed in a heating block and heated at 80° Celsius. After 6 h the mixture was cooled to RT and transferred to a round-bottomed flask and concentrated to dryness. The resulting residue was then partitioned between water (10 mL, ˜pH 3) and DCM (10 mL) with stirring for 1 h at RT. The organic layer was separated, concentrated to dryness and purified by FCC to provide 65.3 mg of the title compound. MS (ESI): mass calcd. for C33H33N5O4, 563.25; m/z found, 564.2 [M+H]+. (500 MHz; CDCl3) δ 8.70 (s, 2H), 8.37 (d, J=2.2 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.51-7.45 (m, 3H), 7.38 (d, J=8.0 Hz, 1H), 7.13 (d, J=8.1 Hz, 2H), 7.05 (dd, J=8.8, 2.3 Hz, 1H), 6.82 (d, J=2.3 Hz, 1H), 5.39-5.29 (m, 2H), 5.14 (s, 2H), 4.07 (s, 3H), 3.20 (d, J=11.3 Hz, 1H), 3.07 (s, 1H), 2.58 (d, J=10.9 Hz, 1H), 2.30 (s, 3H), 1.91-1.59 (m, 5H), 1.45 (q, J=12.4, 11.7 Hz, 2H).

Workup

  1. customThe vial was flushed with N2
  2. customthen capped
  3. temperatureAfter 6 h the mixture was cooled to RT
  4. customtransferred to a round-bottomed flask
  5. concentrationconcentrated to dryness
  6. customThe resulting residue was then partitioned between water (10 mL, ˜pH 3) and DCM (10 mL)
  7. customThe organic layer was separated
  8. concentrationconcentrated to dryness
  9. custompurified by FCC

Sources & evidence

ORD record
ord-3f504c4a4c494d14a20af660872a9eb3
Source dataset
uspto-grants-2015_02
Patent number
US08952177B2

Reaction notes

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