Acetic Acid → HCID 86682415, compound

HRID 2365265Notes

Reaction equation

HRID 2365265 reaction equation
[Si]([O:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[N:15]1[CH:27]([CH2:28][CH:29]=O)[C:26]2[C:17](=[CH:18][C:19]([CH2:31][C:32]3[CH:33]=[N:34][C:35]([Cl:38])=[CH:36][CH:37]=3)=[C:20]3[C:25]=2[N:24]=[CH:23][CH:22]=[CH:21]3)[C:16]1=[O:39])(C(C)(C)C)(C)C.[CH3:40][NH:41][CH3:42].C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCCl>[Cl:38][C:35]1[N:34]=[CH:33][C:32]([CH2:31][C:19]2[CH:18]=[C:17]3[C:16](=[O:39])[N:15]([C@H:10]4[CH2:11][CH2:12][CH2:13][CH2:14][C@@H:9]4[OH:8])[CH:27]([CH2:28][CH2:29][N:41]([CH3:42])[CH3:40])[C:26]3=[C:25]3[C:20]=2[CH:21]=[CH:22][CH:23]=[N:24]3)=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 5003444Sodium cyanoborohydrideHCID 86682413HCID 86682413, compound

Product 1

HCID 86682415HCID 86682415, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of {8-[(1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl]-5-[(6-chloropyridin-3-yl)methyl]-7-oxo-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-9-yl}acetaldehyde (see Example 22, 0.033 g, 0.058 mmol) in 1.2 mL of 1,2-dichloroethane was added dimethylamine (2 M in tetrahydrofuran, 0.059 mL, 0.12 mmol), acetic acid (0.0034 mL, 0.058 mmol), sodium cyanoborohydride (3.7 mg, 0.058 mmol), and 4 Å molecular sieves. The mixture was irradiated in a microwave reactor at 100° C. for 20 min, cooled to ambient temperature, and filtered. The filtrate was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in 2 mL of dichloromethane and treated with hydrochloric acid (6 M aqueous, 4 drops). After 14 hr, the mixture was diluted with dichloromethane, washed 2× with saturated aqueous sodium bicarbonate, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 479.2200 for [M+H]+ [calc'd for C27H32CN4O2, [M+H]+=479.2208]: 1H NMR (400 MHz, CDCl3) δ 8.97-8.96 (m, 1H), 8.34-8.28 (m, 2H), 7.78 (s, 1H), 7.54-7.50 (m, 1H), 7.44-7.40 (m, 1H), 7.24 (d, J=8.3 Hz, 1H), 5.21-5.19 (m, 1H), 4.69-4.51 (m, 1H), 4.47 (s, 2H), 3.42-3.33 (m, 1H), 3.29-3.15 (m, 2H), 2.76-2.63 (m, 1H), 2.49 (s, 6H), 2.29-2.17 (m, 2H), 1.81-1.68 (m, 2H), 1.48-1.00 (m, 5H) ppm.

Workup

  1. customThe mixture was irradiated in a microwave reactor at 100° C. for 20 min
  2. filtrationfiltered
  3. additionThe filtrate was diluted with ethyl acetate
  4. washwashed with saturated aqueous sodium bicarbonate
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe combined organic extracts were dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in 2 mL of dichloromethane
  10. additiontreated with hydrochloric acid (6 M aqueous, 4 drops)
  11. additionthe mixture was diluted with dichloromethane
  12. washwashed 2× with saturated aqueous sodium bicarbonate
  13. dry with materialdried with sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe residue was purified via preparative reverse phase HPLC

Sources & evidence

ORD record
ord-5b0bf48a9f974c1395e4cffad72d76d5
Source dataset
uspto-grants-2014_04
Patent number
US08697690B2

Reaction notes

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