Hydrochloric Acid → racemic cis-2-{1-[4-(5-Chloropyrimidin-2-yl)benzyl]-6-[(5-methylpyridin-2-yl)methoxy]-1H-benzimidazol-2-yl}cyclohexanecarboxylic acid

HRID 1848722Notes

Reaction equation

HRID 1848722 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:33]=[CH:32][C:11]([CH2:12][NH:13][C:14]3[CH:19]=[C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=4)[CH:17]=[CH:16][C:15]=3[N+:29]([O-])=O)=[CH:10][CH:9]=2)=[N:6][CH:7]=1.[C:34]1(=[O:44])[C@@H:42]2[C@@H:37]([CH2:38][CH2:39][CH2:40][CH2:41]2)[C:36](=O)[O:35]1.S(S([O-])=O)([O-])=O.[Na+].[Na+].Cl.C([O-])(O)=O.[Na+]>O.C(Cl)Cl.CC(N(C)C)=O>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:33]=[CH:32][C:11]([CH2:12][N:13]3[C:14]4[CH:19]=[C:18]([O:20][CH2:21][C:22]5[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=5)[CH:17]=[CH:16][C:15]=4[N:29]=[C:36]3[C@H:37]3[CH2:38][CH2:39][CH2:40][CH2:41][C@H:42]3[C:34]([OH:44])=[O:35])=[CH:10][CH:9]=2)=[N:6][CH:7]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 24489Sodium DithioniteHCID 516892Sodium BicarbonateHCID 641660Hexahydrophthalic anhydride, cis-HCID 90411558N-(4-(5-Chloropyrimidin-2-yl)benzyl)-5-((5-methylpyridin-2-yl)methoxy)-2-nitroaniline

Product 1

HCID 86269906racemic cis-2-{1-[4-(5-Chloropyrimidin-2-yl)benzyl]-6-[(5-methylpyridin-2-yl)methoxy]-1H-benzimidazol-2-yl}cyclohexanecarboxylic acidYield 28%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
50 °C

Procedure

In a 5 mL microwave vial were added N-(4-(5-chloropyrimidin-2-yl)benzyl)-5-((5-methylpyridin-2-yl)methoxy)-2-nitroaniline (59 mg, 0.13 mmol), cis-hexahydroisobenzofuran-1,3-dione (33 mg, 0.21 mmol), sodium dithionite (69 mg, 0.39 mmol), DMA (1 mL) and water (0.2 mL). The resulting mixture was heated to 50° Celsius for 16 h. The mixture was cooled to RT, diluted with water (10 mL) and pH adjusted to ˜1 with HCl (1M). To the mixture was added DCM (1 mL) and the pH was adjusted to ˜3 with saturated NaHCO3 (10 mL). The organic layer was separated, concentrated to dryness and the residue was purified using FCC to provide 20.7 mg of the title compound. MS (ESI): mass calcd. for C32H30ClN5O3, 567.20; m/z found, 569.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.76-8.71 (s, 2H), 8.39-8.31 (m, 3H), 7.66-7.59 (d, J=8.9, 1H), 7.50-7.43 (dd, J=8.0, 1.7, 1H), 7.39-7.32 (d, J=8.0, 1H), 7.15-7.08 (m, 2H), 7.07-7.00 (dd, J=8.9, 2.3, 1H), 6.85-6.79 (d, J=2.3, 1H), 5.41-5.27 (m, 2H), 5.18-5.13 (s, 2H), 3.22-3.14 (m, 1H), 3.07-3.03 (m, 1H), 2.61-2.51 (m, 1H), 2.30-2.25 (s, 3H), 1.89-1.55 (m, 5H), 1.49-1.35 (m, 2H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. customThe organic layer was separated
  3. concentrationconcentrated to dryness
  4. customthe residue was purified

Sources & evidence

ORD record
ord-1113e513fff34a7b913b063bd8faa003
Source dataset
uspto-grants-2015_02
Patent number
US08952177B2

Reaction notes

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