2-Amino-3-methylpyridine → phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-{[(3-methyl-2-pyridinyl)amino]carbonyl}-1-pyrazolidinecarboxylate

HRID 1396870Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1396870
[CH:1]1([CH2:6][C@H:7]([CH2:28][N:29]([CH:38]=[O:39])[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:8]([N:10]2[CH:14]([C:15]([OH:17])=O)[CH2:13][CH2:12][N:11]2[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[NH2:61][C:62]1[C:67]([CH3:68])=[CH:66][CH:65]=[CH:64][N:63]=1>C1(C[C@H](CN(C=O)OCC2C=CC=CC=2)C(N2[C@H](C(O)=O)CCN2C(OCC2C=CC=CC=2)=O)=O)CCCC1.O1CCCC1.CN(C1C=CN=CC=1)C>[CH:1]1([CH2:6][C@H:7]([CH2:28][N:29]([CH:38]=[O:39])[O:30][CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:8]([N:10]2[C@H:14]([C:15]([NH:61][C:62]3[C:67]([CH3:68])=[CH:66][CH:65]=[CH:64][N:63]=3)=[O:17])[CH2:13][CH2:12][N:11]2[C:18]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[O:19])=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Komponenten

8

Edukt 4

HCID 153472-Amino-3-methylpyridineHCID 81531DiisopropylethylamineHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 867063412-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

Produkt 1

HCID 86706345phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-{[(3-methyl-2-pyridinyl)amino]carbonyl}-1-pyrazolidinecarboxylateAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 86706346(3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acidLösungsmittel

Versuchsvorschrift

To a solution of 2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidine carboxylic acid (as a mixture of diastereomers enriched in (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid) (250 mg, 0.465 mmol) in tetrahydrofuran (3 ml) was added N,N-diisopropylethylamine (405 μl, 2.325 mmol) and 2,4,6-trichlorobenzoyl chloride (0.087 mL, 0.558 mmol). The mixture was stirred for 2 h and then the solvent was evaporated. The residue was then diluted with toluene (3 mL). The resulting suspension was treated with 2-amino-3-methylpyridine (61 mg, 0.56 mmol) followed by DMAP (11.3 mg, 0.093 mmol). After 2 h, 15 minutes, the solvent mixture was removed. The residue was diluted with MeOH and purified by reverse-phase HPLC to afford 179 mg (61%) of the title compound as a white solid. LC/MS: (M+H)+: 628.5.

Aufarbeitung

  1. customthe solvent was evaporated
  2. additionThe residue was then diluted with toluene (3 mL)
  3. waitAfter 2 h
  4. custom15 minutes, the solvent mixture was removed
  5. additionThe residue was diluted with MeOH
  6. custompurified by reverse-phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-52bae5b85c8f48c2921cce34d89e6ef6
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901119B2

Notizen zur Reaktion

Wird geladen…