Diisopropylethylamine → HCID 178492713, Verbindung

HRID 1676840

Reaktionsgleichung

Reaktionsgleichung von HRID 1676840
[F:1][C:2]1([F:30])[CH2:8][N:7]([CH:9]([CH3:11])[CH3:10])[C:6]2[N:12]=[C:13]([NH:16][C:17]3[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][C:18]=3[O:26][CH3:27])[N:14]=[CH:15][C:5]=2[N:4]([CH3:28])[C:3]1=[O:29].C(N(C(C)C)C(C)C)C.[CH:40]1([CH2:43][N:44]2[CH2:49][CH2:48][N:47]([CH:50]3[CH2:55][CH2:54][CH:53]([NH2:56])[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH2:42][CH2:41]1>CN(C)C=O>[CH:40]1([CH2:43][N:44]2[CH2:49][CH2:48][N:47]([C@@H:50]3[CH2:55][CH2:54][C@H:53]([NH:56][C:21](=[O:22])[C:20]4[CH:24]=[CH:25][C:17]([NH:16][C:13]5[N:14]=[CH:15][C:5]6[N:4]([CH3:28])[C:3](=[O:29])[C:2]([F:30])([F:1])[CH2:8][N:7]([CH:9]([CH3:10])[CH3:11])[C:6]=6[N:12]=5)=[C:18]([O:26][CH3:27])[CH:19]=4)[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH2:41][CH2:42]1.[CH:40]1([CH2:43][N:44]2[CH2:49][CH2:48][N:47]([C@H:50]3[CH2:55][CH2:54][C@H:53]([NH:56][C:21](=[O:22])[C:20]4[CH:24]=[CH:25][C:17]([NH:16][C:13]5[N:14]=[CH:15][C:5]6[N:4]([CH3:28])[C:3](=[O:29])[C:2]([F:30])([F:1])[CH2:8][N:7]([CH:9]([CH3:10])[CH3:11])[C:6]=6[N:12]=5)=[C:18]([O:26][CH3:27])[CH:19]=4)[CH2:52][CH2:51]3)[CH2:46][CH2:45]2)[CH2:41][CH2:42]1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 11586738trans-4-(4-(Cyclopropylmethyl)piperazin-1-yl)cyclohexanamineHCID 445467354-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid

Produkt 2

HCID 178492713HCID 178492713, VerbindungHCID 178492714HCID 178492714, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of 0.08 g (0.19 mmole) of 4-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid (I-292), 0.20 mL (1.2 mmole) of ethyldiisopropyl amine and 0.072 mg (0.21 mmole) of a cis/trans mixture of 4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexylamine with trihydrochloride in 2.0 mL of dimethylformamide was added 0.090 g (0.21 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 dichloromethane-methanol (gradient, 100:0-70:30) gave 0.024 g of N-[cis-4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexyl]-4-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzamide (I-301) (Rf: 0.58 in dichloromethane:methanol 7:3) as a white solid and 0.061 g of N-[trans-4-(4-cyclopropylmethyl-piperazin-1-yl)-cyclohexyl]-4-(7,7-difluoro-9-isopropyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzamide (I-302) (Rf: 0.46 in dichloromethane:methanol 7:3) 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 dichloromethane-methanol (gradient, 100:0-70:30)

Quellen und Nachweise

ORD-Eintrag
ord-23ba99b3deb248599a33c9f3fcebe755
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003785B2

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