Acetic Acid → HCID 59556608, compound

HRID 1172973Notes

Reaction equation

HRID 1172973 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=3)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[CH3:25][C:26]1([CH3:33])[O:30][CH:29]([CH2:31][NH2:32])[CH2:28][O:27]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:18]=[CH:19][C:20]([CH2:21][NH:32][CH2:31][CH:29]4[CH2:28][O:27][C:26]([CH3:33])([CH3:25])[O:30]4)=[CH:23][CH:24]=3)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 41223491,3-Dioxolane-4-methanamine, 2,2-dimethyl-HCID 5003444Sodium cyanoborohydrideHCID 59556538HCID 59556538, compound

Product 1

HCID 59556608HCID 59556608, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)benzaldehyde (150 mg, 0.438 mmol), (2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (0.057 mL, 0.438 mmol), methanol (4 mL), and acetic acid (0.125 mL, 2.188 mmol) were loaded into a 25 mL flask equipped with a stirring bar. The mixture was stirred for about 10 minutes at room temperature under nitrogen. Sodium cyanoborohydride (27.5 mg, 0.438 mmol) was added in one portion, and the reaction mixture was stirred at room temperature overnight. Solvent was removed under reduced pressure and crude material was purified by RP-HPLC (A=50 mM ammonium acetate, B=ACN; 40% to 80% B over 30 min at 21.0 mL/min; UV λ=254 nm; Thermo Hyperprep HS C18, 8 μm, 250×21.2 mm column). Fractions containing product were combined, rotovapped and lyophilized to give N-(4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)benzyl)-1-(2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (130.9 mg, 64.7%) as a white solid. LCMS (Table 1, Method c) Rt=2.59 min, m/z 458.62 (M+H)+; 1H NMR (400 MHz, DMSO) δ ppm 8.13 (d, 2H), 8.06 (d, 1H), 8.00 (dd, 1H), 7.61 (d, 2H), 7.39 (d, 1H), 4.82 (sept, 1H), 4.15 (p, 1H), 3.99 (dd, 1H), 3.84 (s, 2H), 3.63 (dd, 1H), 2.61 (ddd, 2H), 1.86 (s, 4H), 1.35 (d, 6H) 1.26 (s, 3H).

Workup

  1. customequipped with a stirring bar
  2. stirringthe reaction mixture was stirred at room temperature overnight
  3. customSolvent was removed under reduced pressure and crude material
  4. customwas purified by RP-HPLC (A=50 mM ammonium acetate, B=ACN
  5. wait40% to 80% B over 30 min at 21.0 mL/min
  6. additionFractions containing product

Sources & evidence

ORD record
ord-c98ac36af92443ee90472df889f38c39
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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