Trifluoroacetic acid → HCID 178492708, Verbindung

HRID 1044113

Reaktionsgleichung

Reaktionsgleichung von HRID 1044113
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]3([CH2:16][CH2:15][CH2:14]3)[CH2:8][N:7]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:6]=2[N:22]=1.[NH2:23][C:24]1[CH:48]=[CH:47][C:27]([C:28]([NH:30][C@H:31]2[CH2:36][CH2:35][C@H:34]([N:37]3[CH2:42][CH2:41][N:40]([CH2:43][CH:44]4[CH2:46][CH2:45]4)[CH2:39][CH2:38]3)[CH2:33][CH2:32]2)=[O:29])=[CH:26][C:25]=1[O:49][CH3:50].C(O)(C(F)(F)F)=O>>[CH:17]1([N:7]2[CH2:8][C:9]3([CH2:16][CH2:15][CH2:14]3)[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:23][C:24]4[CH:48]=[CH:47][C:27]([C:28]([NH:30][C@H:31]5[CH2:32][CH2:33][C@H:34]([N:37]6[CH2:42][CH2:41][N:40]([CH2:43][CH:44]7[CH2:46][CH2:45]7)[CH2:39][CH2:38]6)[CH2:35][CH2:36]5)=[O:29])=[CH:26][C:25]=4[O:49][CH3:50])=[N:22][C:6]2=3)[CH2:21][CH2:20][CH2:19][CH2:18]1

Komponenten

4

Edukt 3

HCID 6422Trifluoroacetic acidHCID 579698622'-Chloro-9'-cyclopentyl-5'-methyl-8',9'-dihydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepin]-6'(5'H)-one2×HCID 178492706HCID 178492706, Verbindung2×

Produkt 1

HCID 178492708HCID 178492708, Verbindung

Versuchsvorschrift

2′-Chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclobutane-1,7′-pyrimido[4,5-b][1,4]diazepin]-6′(5′H)-one (Intermediate 4) (0.065 g, 0.2 mmol, 1 eq), 4-amino-N-(trans-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide (Intermediate 11) (0.24 g, 0.6 mmol, 3 eq) and TFA (75 μL, 1 mmol, 5 eq) in TFE (6 mL) were heated to reflux together 40 hours. RM was concentrated in vacuo and the residue was partitioned between EtOAc and saturated sodium hydrogen carbonate. The organic layer was separated, washed with saturated brine and concentrated in vacuo to a residue that was purified by preparative RP-HPLC-MS (Preparative—1) to give 4-(9′-cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclobutane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-N-((trans)-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide.

Aufarbeitung

  1. temperatureto reflux together 40 hours
  2. concentrationRM was concentrated in vacuo
  3. customthe residue was partitioned between EtOAc and saturated sodium hydrogen carbonate
  4. customThe organic layer was separated
  5. washwashed with saturated brine
  6. concentrationconcentrated in vacuo to a residue that
  7. customwas purified by preparative RP-HPLC-MS (Preparative—1)

Quellen und Nachweise

ORD-Eintrag
ord-36e7f2ec865a4bbb9042243c22b2d8ec
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08563542B2

Verknüpfte Notizen

Wird geladen…