Diisopropylethylamine → 4-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1676616Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676616
[CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)C(C)C)C.[NH2:42][CH:43]1[CH2:48][CH2:47][N:46]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:45][CH2:44]1>CN(C)C=O>[C:52]([O:51][C:49]([N:46]1[CH2:45][CH2:44][CH:43]([NH:42][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][C:22]([NH:21][C:19]3[N:18]=[CH:17][C:8]4[N:9]([CH3:16])[C:10](=[O:15])[C:11]([F:13])([F:14])[CH2:12][N:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[C:7]=4[N:20]=3)=[C:23]([O:31][CH3:32])[CH:24]=2)[CH2:48][CH2:47]1)=[O:50])([CH3:55])([CH3:54])[CH3:53]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 252529054-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid

Produkt 1

HCID 445487694-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoylamino]-piperidine-1-carboxylic acid tert-butyl esterAusbeute 59,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of 0.25 g (0.56 mmole) of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-22), 0.30 mL (1.7 mmole) of ethyldiisopropyl amine and 0.12 g (0.62 mmole) of 4-amino-1-Boc-piperidine in 4.0 mL of dimethylformamide was added 0.27 g (0.62 mmole) of 1-(di-1-pyrrolidinylmethylene)-1H-benzotriazolium 3-oxide hexafluorophosphate. The mixture was stirred at room temperature for 1 hour, then diluted with 10 mL of ice water. The resulting solid was collected by filtration, washed with saturated sodium carbonate and water, and dried under vacuum. Purification by silica gel chromatography, eluting with hexane-ethylacetate (gradient, 70:30-0:100) gave 0.21 g of 4-[4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester (I-71) as a white solid.

Aufarbeitung

  1. filtrationThe resulting solid was collected by filtration
  2. washwashed with saturated sodium carbonate and water
  3. customdried under vacuum
  4. customPurification by silica gel chromatography
  5. washeluting with hexane-ethylacetate (gradient, 70:30-0:100)

Quellen und Nachweise

ORD-Eintrag
ord-ce88a9adeee64305807cd61c1d75e55e
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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