1-Hydroxybenzotriazole → methyl 4-((2S,4S)-1-(2-(2-methylphenylamino)-6-benzoxazolylacetyl)-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoate

HRID 1372584Notes

Reaction equation

HRID 1372584 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[O:10][C:11]2[CH:17]=[C:16]([CH2:18][C:19](O)=[O:20])[CH:15]=[CH:14][C:12]=2[N:13]=1.[CH:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][C:23]=1[O:32][C@@H:33]1[CH2:37][NH:36][C@H:35]([CH2:38][O:39][C:40]2[CH:49]=[CH:48][C:43]([C:44]([O:46][CH3:47])=[O:45])=[CH:42][CH:41]=2)[CH2:34]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(N(CC)CC)C>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[O:10][C:11]2[CH:17]=[C:16]([CH2:18][C:19]([N:36]3[CH2:37][C@@H:33]([O:32][C:23]4[CH:24]=[CH:25][C:26]5[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=5)[CH:22]=4)[CH2:34][C@H:35]3[CH2:38][O:39][C:40]3[CH:49]=[CH:48][C:43]([C:44]([O:46][CH3:47])=[O:45])=[CH:42][CH:41]=3)=[O:20])[CH:15]=[CH:14][C:12]=2[N:13]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16093586methyl 4-((2S,4S)-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoateHCID 235083152-(2-(O-tolylamino)benzo[d]oxazol-6-yl)acetic acid

Product 1

HCID 58778786methyl 4-((2S,4S)-1-(2-(2-methylphenylamino)-6-benzoxazolylacetyl)-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

In DMF (10 ml), a mixture of 2-(2-methylphenylamino)-6-benzoxazolylacetic acid (141 mg, 0.50 mmol), methyl 4-((2S,4S)-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoate (189 mg, 0.50 mmol), EDC•HCl (144 mg, 0.75 mmol), HOBt (101 mg, 0.75 mmol) and triethylamine was stirred at room temperature for 16 hours. The reaction mixture was poured in ice water (30 ml), followed by extraction with ethyl acetate. The extract was washed with ice water and saturated brine, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was separated and purified by chromatography on a thin-layer silica gel column with (chloroform/acetone (5/1)), whereby the title compound (312 mg, 97%) was obtained as a colorless amorphous substance.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe extract was washed with ice water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationdistilled under reduced pressure
  5. customto remove the solvent
  6. customThe residue was separated
  7. custompurified by chromatography on a thin-layer silica gel column with (chloroform/acetone (5/1)), whereby the title compound (312 mg, 97%)
  8. customwas obtained as a colorless amorphous substance

Sources & evidence

ORD record
ord-571551649c834e849877cb510de73a2a
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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