Formaldehyde → HCID 44548576, compound

HRID 1512912Notes

Reaction equation

HRID 1512912 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[NH:24][CH:23]=[C:22]4[CH:26]=O)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[NH2:28][C@@H:29]([C:31]([O:33]C)=[O:32])[CH3:30].[BH-](OC(C)=O)(OC(C)=O)O[C:37](C)=O.[Na+].C=O>C(Cl)Cl.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[NH:24][CH:23]=[C:22]4[CH2:26][N:28]([CH3:37])[C@@H:29]([C:31]([OH:33])=[O:32])[CH3:30])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 89020methyl D-alaninateHCID 5049666Sodium triacetoxyborohydrideHCID 591461517-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carbaldehyde

Product 1

HCID 44548576HCID 44548576, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carbaldehyde (D61) (150 mg), methyl D-alaninate (81 mg) and acetic acid (24 mg) in DCM (10 mL) was added NaBH(OAc)3 (167 mg). The mixture was stirred at 40° C. for 2 h, followed by addition of formaldehyde (120 mg). This mixture was stirred at 40° C. overnight. After concentration, the residue was dissolved in THF (5 mL), followed by addition of aqueous NaOH (2 M, 2 mL). The mixture was stirred at 50° C. for 2 h, and then acidified with HCl (2 M) to pH 4-5, partitioned between ethyl acetate (25 mL) and water (25 mL). The organic phase was washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulphate, and evaporated to give the crude product, which was purified by Mass Directed Auto Prep to afford N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-N-methyl-D-alanine (E53) (35 mg). δH (DMSO-d6, 400 MHz): 1.30 (3H, d), 1.36 (6H, d), 2.42 (3H, s), 3.40 (1H, q), 4.16 (2H, s), 4.90 (1H, m), 7.26 (1H, t), 7.45 (1H, d), 7.56 (1H, d), 7.97 (1H, d), 8.09 (1H, d), 8.21 (1H, dd), 8.38 (1H, d), 11.17 (1H, br s). MS (ES): C24H25ClN4O4 requires 468; found 366.1 (M—C4H8NO2+).

Workup

  1. stirringThis mixture was stirred at 40° C. overnight
  2. concentrationAfter concentration
  3. dissolutionthe residue was dissolved in THF (5 mL)
  4. additionfollowed by addition of aqueous NaOH (2 M, 2 mL)
  5. stirringThe mixture was stirred at 50° C. for 2 h
  6. custompartitioned between ethyl acetate (25 mL) and water (25 mL)
  7. washThe organic phase was washed with water (25 mL) and brine (25 mL)
  8. dry with materialdried over anhydrous sodium sulphate
  9. customevaporated
  10. customto give the crude product, which
  11. customwas purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-cd56d7de5fab4be08135e310740645b5
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

Loading…