Triethylamine → Methyl 4-((2S,4S)-1-(7-fluoro-2-(2-methylphenylamino)-6-benzoxazolylacetyl)-4-fluoro-2-pyrrolidinylmethoxy)benzoate

HRID 1372575Notes

Reaction equation

HRID 1372575 reaction equation
[F:1][C:2]1[C:10]2[O:9][C:8]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:18])=[N:7][C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:19][C:20](O)=[O:21].[F:23][C@@H:24]1[CH2:28][NH:27][C@H:26]([CH2:29][O:30][C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=2)[CH2:25]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[F:1][C:2]1[C:10]2[O:9][C:8]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:18])=[N:7][C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:19][C:20]([N:27]1[CH2:28][C@@H:24]([F:23])[CH2:25][C@H:26]1[CH2:29][O:30][C:31]1[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=1)=[O:21]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16093588HCID 16093588, compoundHCID 44606816HCID 44606816, compound

Product 1

HCID 58778812Methyl 4-((2S,4S)-1-(7-fluoro-2-(2-methylphenylamino)-6-benzoxazolylacetyl)-4-fluoro-2-pyrrolidinylmethoxy)benzoateYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In DMF (5 ml), 7-fluoro-2-(2-methylphenylamino)-6-benzoxazolylacetic acid (300 mg, 1.0 mmol), methyl 4-((2S,4S)-4-fluoro-2-pyrrolidinylmethoxy)benzoate (253 mg, 1.0 mmol), EDC•HCl (288 mg, 1.5 mmol), HOBt (203 mg, 1.5 mmol) and triethylamine (0.70 ml, 5.0 mmol) were stirred at room temperature for 14 hours. After the reaction mixture was poured in ice water (20 ml), the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column (silica gel: 50 g), whereby from chloroform/acetone (10/1) eluate fractions, the title compound (490 mg, 92%) was obtained as a colorless amorphous substance.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationdistilled under reduced pressure
  5. customto remove the solvent
  6. customThe residue was purified by chromatography on a silica gel column (silica gel: 50 g), whereby from chloroform/acetone (10/1) eluate fractions

Sources & evidence

ORD record
ord-595daef799d44cea8e5ff0e72d5d9ce2
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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