L-Tartaric acid → 2-Amino-N-{1-(2,4-difluoro-benzyloxymethyl)-2-oxo-2-[3-oxo-3a-pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethyl}-2-methyl-propionamide L-(+) tartrate

HRID 986994Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 986994
[NH2:1][C:2]([CH3:43])([CH3:42])[C:3]([NH:5][CH:6]([CH2:31][O:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=1[F:41])[C:7](=[O:30])[N:8]1[CH2:13][CH2:12][C:11]2=[N:14][N:15]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:16](=[O:17])[C:10]2([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[CH2:9]1)=[O:4].[C:44]([OH:53])(=[O:52])[C@@H:45]([C@H:47]([C:49]([OH:51])=[O:50])[OH:48])[OH:46]>CO>[C:49]([C@@H:47]([C@H:45]([C:44]([OH:53])=[O:52])[OH:46])[OH:48])([OH:51])=[O:50].[NH2:1][C:2]([CH3:43])([CH3:42])[C:3]([NH:5][CH:6]([CH2:31][O:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][C:35]=1[F:41])[C:7](=[O:30])[N:8]1[CH2:13][CH2:12][C:11]2=[N:14][N:15]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:16](=[O:17])[C:10]2([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[CH2:9]1)=[O:4]

Komponenten

4

Edukt 2

HCID 444305L-Tartaric acidHCID 221374552-Amino-N-(1-(2,4-difluoro-benzyloxymethyl)-2-oxo-2-[3-oxo-3a-pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethyl]-2-methyl-propionamide

Produkt 1

HCID 867585022-Amino-N-{1-(2,4-difluoro-benzyloxymethyl)-2-oxo-2-[3-oxo-3a-pyridin-2-ylmethyl-2-(2,2,2-trifluoro-ethyl)-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethyl}-2-methyl-propionamide L-(+) tartrateAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel2×

Reaktionsbedingungen

Temperatur
22 °C

Versuchsvorschrift

To a solution of product from step I (370 g, 0.6 mol) in methanol (4,070 mL) in a 12 L round bottom flask equipped with a mechanical stirrer was added L-(+) tartaric acid (90 g, 0.6 mol). The reaction mixture was stirred for about 90 min. at about 22° C., filtered and concentrated. The crude residue was diluted with ethyl acetate (4,560 mL), heated at about 70° C. and slowly allowed to cool to room temperature over about 17 hours. The solid was filtered and dried to give white crystals, mp 188-189° C. (348.46 g, yield 76%). 1H NMR (MeOH, d4) δ: 8.28 (d, 1H), 7.59 (t, 1H), 7.41-7.39 (m, 1H), 7.18-7.13 (m, 1H), 6.92 (t, 1H), 5.2 (t, 1H), 4.56 (bs, 3H), 4.36 (s, 2H), 4.31-4.25 (m, 1H), 4.13-4.06 (m, 1H), 3.78 (d, 2H), 3.21 (t, 1H), 3.18-2.96 (m, 2H), 2.65-2.55 (m, 2H), 1.57 (d, 6H). MS: MH+611. [a]589 +22.03 (c=11.9, MeOH).

Aufarbeitung

  1. filtrationfiltered
  2. concentrationconcentrated
  3. additionThe crude residue was diluted with ethyl acetate (4,560 mL)
  4. temperatureheated at about 70° C.
  5. temperatureto cool to room temperature over about 17 hours
  6. filtrationThe solid was filtered
  7. customdried
  8. customto give white crystals, mp 188-189° C. (348.46 g, yield 76%)

Quellen und Nachweise

ORD-Eintrag
ord-14ba351cb45146268a89c3f6efc7222e
Quelldatensatz
uspto-grants-2003_10
Patentnummer
US06630487B2

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