Acetaldehyde → HCID 118272016, compound

HRID 590891Notes

Reaction equation

HRID 590891 reaction equation
[NH2:1][C:2]1[C:6]2[C:7]([Cl:23])=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[NH:4][N:3]=1.[CH:24](=O)[CH3:25].C([BH3-])#N.[Na+].Cl>CO>[Cl:23][C:7]1[C:6]2[C:2]([NH:1][CH2:24][CH3:25])=[N:3][NH:4][C:5]=2[CH:10]=[C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])=[O:13])[N:8]=1

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 5003444Sodium cyanoborohydrideHCID 73505860HCID 73505860, compound

Product 1

HCID 118272016HCID 118272016, compoundYield 32.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of (R)-1-(3-amino-4-chloro-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (0.06 g, 0.18 mmol) in methanol (2.0 mL) was added aqueous acetaldehyde (0.025 mL, 35 wt. % in water, 0.20 mmol) followed by sodium cyanoborohydride (0.03 g, 0.54 mmol) and stirred at room temperature for 12 h. After confirming the completion of reaction by TLC, the reaction mixture was acidified with 1.5 N HCl and concentrated under reduced pressure. The crude product was dissolved in ethyl acetate, washed with 10% NaOH followed by water and brine solution. The organic layer was concentrated under reduced pressure and crude product was purified by preparative HPLC to afford (R)-1-(4-chloro-3-(ethylamino)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (0.021 g, 32.0%). 1H NMR (ppm, 400 MHz, DMSO-d6): δ 11.92 (s, 1H), 9.05 (s, 1H), 7.44 (s, 1H), 7.37-7.32 (m, 4H), 7.26-7.22 (m, 2H), 5.44 (t, J=5.6 Hz, 1H), 4.84 (m, 1H), 3.28-3.23 (m, 2H), 1.39 (d, J=8.00 Hz, 3H), 1.20 (t, J=6.8 Hz, 3H). MS ES calc'd. for C17H19ClN6O2 [M+H]+ 359. Found: 359.

Workup

  1. customthe completion of reaction by TLC
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe crude product was dissolved in ethyl acetate
  4. washwashed with 10% NaOH
  5. concentrationThe organic layer was concentrated under reduced pressure and crude product
  6. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-6022587816b549a9ab854e3cc4a0e968
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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