Diisopropylethylamine → Phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)hexanoyl]-1-pyrazolidinecarboxylate

HRID 1396961Notes

Reaction equation

HRID 1396961 reaction equation
[CH:1]([N:3]([CH2:12][C@@H:13]([CH2:34][CH2:35][CH2:36][CH3:37])[C:14]([N:16]1[C@H:20]([C:21](O)=[O:22])[CH2:19][CH2:18][N:17]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])=[O:15])[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:2].ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.CCN(C(C)C)C(C)C.[F:59][C:60]1[CH:61]=[CH:62][C:63]([NH2:66])=[N:64][CH:65]=1>C1COCC1.CN(C1C=CN=CC=1)C.CCOC(C)=O>[F:59][C:60]1[CH:61]=[CH:62][C:63]([NH:66][C:21]([C@@H:20]2[CH2:19][CH2:18][N:17]([C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])[N:16]2[C:14](=[O:15])[C@@H:13]([CH2:12][N:3]([CH:1]=[O:2])[O:4][CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:34][CH2:35][CH2:36][CH3:37])=[O:22])=[N:64][CH:65]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 27377012-Amino-5-fluoropyridineHCID 86706343(3S)-2-[(2R)-2-({Formyl[(phenylmethyl)oxy]amino}methyl)hexanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

Product 1

HCID 86706393Phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)hexanoyl]-1-pyrazolidinecarboxylateYield 19.5%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)hexanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (1 g, 1.95 mmol) in THF (15 mL) under N2 was added 2,4,6-trichlorobenzoyl chloride (0.572 g, 2.34 mmol) and DIPEA (1.68 mL, 9.75 mmol). The mixture was stirred at rt for 2 h. THF was removed under vacuum and toluene (15 mL) was added. To this mixture was added 5-fluoro-2-pyridinamine (0.262 g, 2.34 mmol) and DMAP (47.5 mg, 0.39 mmol). After being stirred at rt overnight, the mixture was diluted with EtOAc (50 mL) and washed with citric acid and brine. The organic solution was dried and concentrated. The residue was purified by flash column chromatography eluting with EA/PE (1:5) to provide the title compound (0.23 g, 19%) as colorless oil.

Workup

  1. customTHF was removed under vacuum and toluene (15 mL)
  2. additionwas added
  3. stirringAfter being stirred at rt overnight
  4. washwashed with citric acid and brine
  5. customThe organic solution was dried
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography
  8. washeluting with EA/PE (1:5)

Sources & evidence

ORD record
ord-ac374e1645c742b6960db1f6c3de1645
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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