Water → (1R,2R)-2-((6-((9H-purin-9-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol

HRID 1848118Notes

Reaction equation

HRID 1848118 reaction equation
[N:1]1[CH:9]=[C:8]2[C:4]([N:5]([CH2:10][C:11]3[CH:22]=[CH:21][C:14]4[N:15]=[C:16](S(C)=O)[O:17][C:13]=4[CH:12]=3)[CH:6]=[N:7]2)=[N:3][CH:2]=1.[NH2:23][C@@H:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]1[OH:30].CCN(C(C)C)C(C)C.O>CC(N(C)C)=O>[N:1]1[CH:9]=[C:8]2[C:4]([N:5]([CH2:10][C:11]3[CH:22]=[CH:21][C:14]4[N:15]=[C:16]([NH:23][C@@H:24]5[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]5[OH:30])[O:17][C:13]=4[CH:12]=3)[CH:6]=[N:7]2)=[N:3][CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 866810906-((9H-purin-9-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole

Product 1

HCID 86681091(1R,2R)-2-((6-((9H-purin-9-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanolYield 54.9%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 6-((9H-purin-9-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole (106 mg, 0.34 mmol), (1R,2R)-2-aminocyclohexanol (77 mg, 0.51 mg) and DIEA (132 mg, 1.02 mmol) in DMA (3 mL) was stirred at 135° C. for 2 h. The reaction mixture was cooled to rt, poured into water (30 mL) and extracted with ethyl acetate (20 mL×2). 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 1:6 petroleum ether/ethyl acetate to give crude product, which was washed with 10:1 petroleum ether/ethyl acetate to afford (1R,2R)-2-((6-((9H-purin-9-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol as a light yellow solid (68 mg, 48.57%). 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.96 (s, 1H), 8.73 (s, 1H), 7.79 (d, J=7.8 Hz, 1H), 7.42 (s, 1H), 7.16 (d, J=1.2 Hz, 1H), 7.14 (d, J=8.1 Hz, 1H) 5.51 (s, 2H), 4.66 (d, J=4.2 Hz, 1H), 3.34 (br s, 2H), 1.90 (br s, 2H), 1.60 (br s, 2H), 1.22 (br s, 4H). LCMS (ESI) m/z 365 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionextracted with ethyl acetate (20 mL×2)
  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 1:6 petroleum ether/ethyl acetate
  9. customto give crude product, which
  10. washwas washed with 10:1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-011841e96ebb4ffba2ad92c6a61f6b93
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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