Acetic Acid → HCID 44548578, compound

HRID 1512914Notes

Reaction equation

HRID 1512914 reaction equation
C([C:3]1[C:11]2[C:6](=[C:7]([C:12]3[N:16]=[C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])[O:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[NH:5][CH:4]=1)=O.[CH3:29][NH:30][CH2:31][C:32]([OH:34])=[O:33].[C:35](O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C:22]([C:21]1[CH:24]=[C:17]([C:15]2[O:14][N:13]=[C:12]([C:7]3[CH:8]=[CH:9][CH:10]=[C:11]4[C:6]=3[NH:5][CH:4]=[C:3]4[CH2:29][N:30]([CH3:35])[CH2:31][C:32]([OH:34])=[O:33])[N:16]=2)[CH:18]=[CH:19][C:20]=1[O:25][CH:26]([CH3:28])[CH3:27])#[N:23]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1088SarcosineHCID 5049666Sodium triacetoxyborohydrideHCID 86637986HCID 86637986, compound

Product 1

HCID 44548578HCID 44548578, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 5-[3-(3-formyl-1H-indol-7-yl)-1,2,4-oxadiazol-5-yl]-2-[(1-methylethyl)oxy]benzonitrile (200 mg), N-methylglycine (96 mg) and acetic acid (32 mg) in DCM (10 mL) was added NaBH(OAc)3 (228 mg). The mixture was stirred at 40° C. overnight. After cooled to room temperature, the reaction mixture was diluted with DCM (10 mL), washed with water (20 mL) and aqueous saturated sodium bicarbonate (20 mL). The organic phase was separated and dried over anhydrous sodium sulphate. After concentration, the residue was purified by Mass Directed Auto Prep to afford N-{[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-N-methylglycine (E55) (140 mg, TFA salt). δH (DMSO-d6, 400 MHz): 1.38 (6H, d), 2.73 (3H, s), 3.80 (2H, s), 4.46 (2H, s), 4.98 (1H, m), 7.31 (1H, t), 7.55 (1H, d), 7.71 (1H, d), 7.98 (1H, d), 8.05 (1H, d), 8.48 (1H, dd), 8.71 (1H, d), 11.41 (1H, br s). MS (ES): C24H23N5O4 requires 445; found 357.2 (M—C3H6NO2+).

Workup

  1. temperatureAfter cooled to room temperature
  2. washwashed with water (20 mL) and aqueous saturated sodium bicarbonate (20 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over anhydrous sodium sulphate
  5. concentrationAfter concentration
  6. customthe residue was purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-87da83a28e3d49aab2917fe7683cc6db
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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