HCID 69286564, compound → HCID 11192300, compound

HRID 2377539Notes

Reaction equation

HRID 2377539 reaction equation
C(OC(=O)[N:10]([CH2:41][C:42]1[CH:47]=[CH:46][C:45]([CH3:48])=[CH:44][C:43]=1[CH3:49])[CH2:11][C@H:12]([NH:18][C:19](=[O:40])[CH2:20][C:21](=[O:39])[NH:22][C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([NH:33][C:34]([NH:36][CH2:37][CH3:38])=[O:35])[CH:24]=1)[C@@H:13]([OH:17])[CH2:14][CH2:15][CH3:16])C1C=CC=CC=1>CO.[Pd]>[CH3:49][C:43]1[CH:44]=[C:45]([CH3:48])[CH:46]=[CH:47][C:42]=1[CH2:41][NH:10][CH2:11][C@H:12]([NH:18][C:19](=[O:40])[CH2:20][C:21]([NH:22][C:23]1[CH:28]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:26]=[C:25]([NH:33][C:34]([NH:36][CH2:37][CH3:38])=[O:35])[CH:24]=1)=[O:39])[C@@H:13]([OH:17])[CH2:14][CH2:15][CH3:16]

Participants

4

Reactant 1

HCID 69286564HCID 69286564, compound

Product 1

HCID 11192300HCID 11192300, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of {(2S,3S)-2-[2-(3-amino-5-trifluoromethyl-phenylcarbamoyl)-acetylamino]-3-hydroxyhexyl}-(2,4-dimethyl-benzyl)-carbamic acid benzyl ester (110 mg, 0.18 mmol, see procedure 12c) in THF (4 mL) was charged with trichloroacetylchloride (0.063 mL, 0.53 mmol). The reaction was stirred for 12 h at RT and concentrated in vacuo. The residue was dissolved in THF (4 mL). The resultant solution was charged with ethylamine (0.175 mL of a 2.0 M solution in THF, 0.35 mmol). The reaction was stirred for 4 h at RT and concentrated in vacuo. The residue was dissolved in EtOAc and washed successively with water and brine. The organic phase was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified via flash chromatography to afford (2,4-dimethyl-benzyl)-[(2S,3S)-2-{2-[3-(3-ethyl-ureido)-5-trifluoromethyl-phenylcarbamoyl]-acetylamino}-3-hydroxy-hexyl]-carbamic acid benzyl ester as an oil (55 mg, 45% yield). MS found: (M+Na)+=722.4. (16b) The compound (2,4-dimethyl-benzyl)-[(2S,3S)-2-{2-[3-(3-ethyl-ureido)-5-trifluoromethyl-phenylcarbamoyl]-acetylamino}-3-hydroxy-hexyl]-carbamic acid benzyl ester was dissolved in MeOH (2 mL). This solution was charged with 5% Pd/C, Degussa style (11 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo. Purification of the residue by reverse-phase HPLC provided the title compound as a white powder after lyopholization. MS found: (M+H)+=566.3.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo
  3. customPurification of the residue by reverse-phase HPLC

Sources & evidence

ORD record
ord-8341551f287b4750be15030d15c46a5b
Source dataset
uspto-grants-2008_12
Patent number
US07468440B2

Reaction notes

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