Water → (1R,2R)-2-((6-((5-bromo-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol

HRID 1848232Notes

Reaction equation

HRID 1848232 reaction equation
[Br:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]2[N:6]([CH2:9][C:10]3[CH:21]=[CH:20][C:13]4[N:14]=[C:15](S(C)=O)[O:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[NH2:25][C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[OH:32].CCN(C(C)C)C(C)C.O>CC(N(C)C)=O>[Br:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]2[N:6]([CH2:9][C:10]3[CH:21]=[CH:20][C:13]4[N:14]=[C:15]([NH:25][C@@H:26]5[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]5[OH:32])[O:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 866812036-((5-bromo-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole

Product 1

HCID 86681204(1R,2R)-2-((6-((5-bromo-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanolYield 91.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-((5-bromo-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole (460 mg, 1.08 mmol), (1R,2R)-2-aminocyclohexanol (245 mg, 2.13 mmol) and DIEA (366 mg, 2.84 mmol) in DMA (10 mL) was stirred at 120° C. for 1 h. The reaction mixture was cooled to rt, poured into water (30 mL) and extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 1:5 petroleum ether/ethyl acetate to give (1R,2R)-2-((6-((5-bromo-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol as a light yellow solid (470 mg, 82.3%). 1H NMR (300 MHz, CDCl3) δ 8.52 (s, 1H), 8.06 (s, 1H), 8.00 (s, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.41 (s, 1H), 7.14 (s, 1H), 5.48 (s, 2H), 4.68 (d, J=4.2 Hz, 1H), 3.33 (br s, 2H), 1.91 (br s, 2H), 1.63 (br s, 2H), 1.25 (br s, 4H). LCMS (ESI) m/z 477 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionextracted with ethyl acetate (100 mL×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 1:5 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-7f02f8c68dc9463cb72a0e1410e4352d
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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