3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → 3-(7-Cyclopropyl-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester

HRID 518985Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 518985
[NH2:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[CH:16]1[CH2:18][CH2:17]1)[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:20])[C:7](=[O:19])[NH:8][N:9]=1.O=[C:22]1[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23]1.C([BH3-])#N.[Na+]>CCO.CC(O)=O>[C:29]([O:28][C:26]([N:24]1[CH2:25][CH:22]([NH:1][C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][C:15]=2[CH:16]2[CH2:17][CH2:18]2)[O:12][CH2:11][C:10]2[N:5]3[CH:6]([CH3:20])[C:7](=[O:19])[NH:8][N:9]=2)[CH2:23]1)=[O:27])([CH3:32])([CH3:30])[CH3:31]

Komponenten

6

Edukt 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5003444Sodium cyanoborohydrideHCID 867273366-Amino-7-cyclopropyl-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

Produkt 1

HCID 867273373-(7-Cyclopropyl-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl esterAusbeute 41,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 702EthanolLösungsmittel

Versuchsvorschrift

A solution of 6-amino-7-cyclopropyl-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.860 g, 3.16 mmol) and tert-butyl 3-oxoazetidine-1-carboxylate (2.703 g, 15.79 mmol) in EtOH (25 mL) and HOAc (2.5 mL) was heated to reflux overnight. The reaction mixture was cooled to ambient temperature and sodium cyanoborohydride (0.073 g, 1.159 mmol) was added. The reaction mixture was stirred overnight and concentrated in vacuo. The residue was purified by preparative HPLC (Table 3, Method 3) to give 3-(7-cyclopropyl-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (0.560 g, 41%). The racemic product was separated by chiral SFC (Table 2, Method 6) to give 3-(7-cyclopropyl-4(R)-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (Enantiomer 1, SFC (Table 1, Method 12) Rt=6.01 min., 0.300 g, 22%) and 3-[7-(2,4-dichloro-phenyl)-4(S)-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester (Enantiomer 2, SFC (Table 1, Method 12) Rt=8.89 min., 0.280 g, 20%).

Aufarbeitung

  1. temperatureto reflux overnight
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by preparative HPLC (Table 3, Method 3)

Quellen und Nachweise

ORD-Eintrag
ord-1377736a7cbb456b8a472f2ae18bddb2
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115151B2

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