Acetic Acid → 7-methoxy-3-(1-{6-[7-methyl-2-(2,2,2-trifluoroethyl)-3H-benzimidazol-5-yloxy]-pyrimidin-4-yl}-piperidin-4-yl)-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

HRID 1846544Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1846544
[NH2:1][C:2]1[CH:3]=[C:4]([CH:32]=[C:33]([CH3:36])[C:34]=1[NH2:35])[O:5][C:6]1[N:11]=[CH:10][N:9]=[C:8]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:24][CH2:23][C:22]4[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:21]=4[NH:20][C:19]3=[O:31])[CH2:14][CH2:13]2)[CH:7]=1.[F:37][C:38]([F:44])([F:43])[CH2:39][C:40](O)=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O)(=O)C>CN(C=O)C>[CH3:30][O:29][C:26]1[CH:27]=[CH:28][C:21]2[NH:20][C:19](=[O:31])[N:18]([CH:15]3[CH2:14][CH2:13][N:12]([C:8]4[CH:7]=[C:6]([O:5][C:4]5[CH:32]=[C:33]([CH3:36])[C:34]6[N:35]=[C:40]([CH2:39][C:38]([F:44])([F:43])[F:37])[NH:1][C:2]=6[CH:3]=5)[N:11]=[CH:10][N:9]=4)[CH2:17][CH2:16]3)[CH2:24][CH2:23][C:22]=2[CH:25]=1

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27779723,3,3-Trifluoropropionic acidHCID 669783753-{1-[6-(3,4-Diamino-5-methyl-phenoxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

Produkt 1

HCID 462446787-methoxy-3-(1-{6-[7-methyl-2-(2,2,2-trifluoroethyl)-3H-benzimidazol-5-yloxy]-pyrimidin-4-yl}-piperidin-4-yl)-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

0.20 g (0.42 mmol) 3-{1-[6-(3,4-diamino-5-methyl-phenoxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one, 60 mg (0.46 mmol) 3,3,3-tri-fluoropropionic acid, 0.15 g (0.47 mmol) TBTU and 0.14 mL (1.0 mmol) TEA in 2.0 mL DMF were stirred for 4 h at RT. Then 2.0 mL glacial acetic acid was added and the mixture was stirred overnight at RT. In addition the reaction mixture was stirred for 1 h at 100° C., then cooled and purified by preparative HPLC-MS. The product-containing fractions were combined and the acetonitrile was evaporated down. The residue was made alkaline with 4N aqueous sodium hydroxide solution, the precipitate formed was suction filtered, washed with water and dried under HV.

Aufarbeitung

  1. additionIn addition the reaction mixture
  2. stirringwas stirred for 1 h at 100° C.
  3. temperaturecooled
  4. custompurified by preparative HPLC-MS
  5. customthe acetonitrile was evaporated down
  6. customthe precipitate formed
  7. filtrationfiltered
  8. washwashed with water
  9. customdried under HV

Quellen und Nachweise

ORD-Eintrag
ord-8fc6965af7b740dfb5091a199cfc16aa
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952014B2

Notizen zur Reaktion

Wird geladen…