Acetic Acid → HCID 58012042, compound

HRID 660955Notes

Reaction equation

HRID 660955 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][C:14]3[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=3)[C:17](O)=[O:18])[C:11](=[O:23])[N:10]([CH2:24][C:25]([NH:27][C:28]([CH3:40])([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=3)[CH3:29])=[O:26])[N:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[BH4-].[Na+].C(O)(=O)C>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:16]([CH2:17][OH:18])[CH:15]=3)[C:11](=[O:23])[N:10]([CH2:24][C:25]([NH:27][C:28]([CH3:40])([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:37])([F:38])[F:39])[CH:31]=3)[CH3:29])=[O:26])[N:9]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 58012040HCID 58012040, compound

Product 1

HCID 58012042HCID 58012042, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

30 mg (0.052 mmol) of 3-(3-(4-chlorophenyl)-1-[2-(1-methyl-1-[3-(trifluoromethyl)phenyl]ethylamino)-2-oxoethyl]-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-ylmethyl)-benzoic acid (Example 471) are dissolved in 2 ml of THF and treated with 24 mg (0.24 mmol) of triethylamine and 33 mg (0.24 mmol) of isobutyl chloroformate. This is stirred for 1 hr at RT. Next, a solution of 24 mg (0.63 mmol) of sodium borohydride in 0.05 ml water is added slowly. After 1 hr, the mixture is treated with 0.06 ml (1.05 mmol) of acetic acid and then concentrated in vacuo. The residue is taken up in 10 ml of ethyl acetate, and washed with 10 ml of water. The aqueous phase is back-extracted once with 10 ml of ethyl acetate. The combined organic phases are dried over sodium sulphate, filtered and concentrated in vacuo. The crude product is purified by preparative HPLC [Method 10]. 23 mg (79% of theory) of the target compound are thus obtained.

Workup

  1. waitAfter 1 hr
  2. concentrationconcentrated in vacuo
  3. washwashed with 10 ml of water
  4. extractionThe aqueous phase is back-extracted once with 10 ml of ethyl acetate
  5. dry with materialThe combined organic phases are dried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by preparative HPLC [Method 10]
  9. custom23 mg (79% of theory) of the target compound are thus obtained

Sources & evidence

ORD record
ord-2b562095374b451a941a8d830a9f7c5a
Source dataset
uspto-grants-2011_12
Patent number
US08084481B2

Reaction notes

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