Acetic Acid → HCID 44549036, compound

HRID 1512927Notes

Reaction equation

HRID 1512927 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[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][CH:28]=O)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[NH:30]1[CH2:37][CH2:36][CH2:35][C@H:31]1[C:32]([OH:34])=[O:33].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[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[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][CH2:28][N:30]3[CH2:37][CH2:36][CH2:35][C@H:31]3[C:32]([OH:34])=[O:33])[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 145742L-ProlineHCID 5049666Sodium triacetoxyborohydrideHCID 59146184HCID 59146184, compound

Product 1

HCID 44549036HCID 44549036, compoundYield 19.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a stirred solution of [7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]acetaldehyde (D88) (50 mg), L-proline (28 mg) and acetic acid (0.1 mL) in DCM (10 mL) stirred at 20° C. was added sodium triacetoxyborohydride (52 mg). The reaction was stirred at 20° C. for 3 h. The mixture was concentrated and the residue was partitioned between ethyl acetate (25 mL) and aqueous HCl (2 M, 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 1-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}-L-proline (E69) (12 mg, TFA salt). δH (DMSO-d6, 400 MHz): 1.35 (6H, d), 1.71 (1H, m), 1.94 (2H, m), 2.16 (1H, m), 2.95 (1H, m), 3.05 (2H, m), 3.25 (2H, m), 3.60 (2H, m), 3.65 (3H, s), 4.88 (1H, m), 7.20 (1H, t), 7.31 (1H, s), 7.45 (2H, m), 7.86 (1H, dd), 8.13 (1H, dd), 8.20 (1H, d). MS (ES): C27H29ClN4O4 requires 508; found 509.2 (M+H+).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between ethyl acetate (25 mL) and aqueous HCl (2 M, 25 mL)
  3. washThe organic phase was washed with water (25 mL) and brine (25 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. customevaporated
  6. customto give the crude product, which
  7. customwas purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-b5194980db2441e8ac9e9eca08274a5f
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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