Formaldehyde → HCID 178462259, compound

HRID 914046Notes

Reaction equation

HRID 914046 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[C:6]([C@H:12]([O:14][CH2:15][C:16]3([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[CH3:13])[CH:7]=[C:8]([Br:11])[CH:9]=2)[NH:4][N:3]=1.C=O.[C:31]([BH3-])#N.[Na+].O>C(#N)C.C(O)(=O)C>[Br:1][C:2]1[C:10]2[C:5](=[C:6]([C@H:12]([O:14][CH2:15][C:16]3([C:22]4[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=4)[CH2:21][CH2:20][N:19]([CH3:31])[CH2:18][CH2:17]3)[CH3:13])[CH:7]=[C:8]([Br:11])[CH:9]=2)[NH:4][N:3]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 178462257HCID 178462257, compound

Product 1

HCID 178462259HCID 178462259, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

(R)-3,5-Dibromo-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-1H-indazole (77 mg, 0.15 mmol) was dissolved in acetonitrile (1 mL) and treated with formalin (50 μL) and sodium cyanoborohydride (9.5 mg, 0.15 mmol) and one drop of acetic acid. The reaction was stirred at room temperature for 1 h. The reaction was poured into water and extracted with diethyl ether. The aqueous was made basic by addition of 4 M sodium hydroxide and extracted with diethyl ether. The ethereal was combined, washed with brine, dried over magnesium sulfate, and concentrated. The resulting residue was dissolved in 20% trifluoroacetic acid in dichloromethane and stirred at room temperature for 5 min. The solution was concentrated, loaded onto a strong cation exchange cartridge in methanol, and the cartridge washed with several volumes of methanol which were discarded. The product was eluted with 2M ammonia in methanol and concentrated to give 41 mg (52%). 1H-NMR (CDCl3, 500 MHz) δ 10.09 (bs, 1H), 7.62 (d, J=1.5 Hz, 1H), 7.24 (dd, J=8.9 Hz, 5.2, 2H), 7.13 (d, J=1.5 Hz, 1H), 7.05 (dd, J=8.9, 8.5 Hz, 2H), 4.49 (q, J=6.7 Hz, 1H), 3.39 (d, J=8.9 Hz, 1H), 3.25 (d, J=8.9 Hz, 1H), 2.59 (m, 2H), 1.85-2.30 (m, 9H), 1.40 (d, J=6.7 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 161.6 (d, J=246 Hz), 137.2, 128.7, 128.63, 128.57, 127.68, 125.3, 121.7, 121.6, 115.7, 115.5, 114.3, 78.9, 77.9, 51.9, 51.7, 46.1, 40.3, 32.6, 32.3, 22.1.

Workup

  1. extractionextracted with diethyl ether
  2. additionThe aqueous was made basic by addition of 4 M sodium hydroxide
  3. extractionextracted with diethyl ether
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. dissolutionThe resulting residue was dissolved in 20% trifluoroacetic acid in dichloromethane
  8. stirringstirred at room temperature for 5 min
  9. concentrationThe solution was concentrated
  10. washthe cartridge washed with several volumes of methanol which
  11. washThe product was eluted with 2M ammonia in methanol
  12. concentrationconcentrated
  13. customto give 41 mg (52%)

Sources & evidence

ORD record
ord-c5c0695488dd40d7bb600f3fe827d81a
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

Loading…