Trifluoroacetic acid → HCID 178492710, Verbindung

HRID 2280029Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2280029
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH2:9][CH2:8][N:7]([CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:6]=2[N:19]=1.[NH2:20][C:21]1[CH:45]=[CH:44][C:24]([C:25]([NH:27][C@H:28]2[CH2:33][CH2:32][C@H:31]([N:34]3[CH2:39][CH2:38][N:37]([CH2:40][CH:41]4[CH2:43][CH2:42]4)[CH2:36][CH2:35]3)[CH2:30][CH2:29]2)=[O:26])=[CH:23][C:22]=1[O:46][CH3:47].C(O)(C(F)(F)F)=O>>[CH:14]1([N:7]2[CH2:8][CH2:9][C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:20][C:21]4[CH:45]=[CH:44][C:24]([C:25]([NH:27][C@H:28]5[CH2:29][CH2:30][C@H:31]([N:34]6[CH2:39][CH2:38][N:37]([CH2:40][CH:41]7[CH2:43][CH2:42]7)[CH2:36][CH2:35]6)[CH2:32][CH2:33]5)=[O:26])=[CH:23][C:22]=4[O:46][CH3:47])=[N:19][C:6]2=3)[CH2:18][CH2:17][CH2:16][CH2:15]1

Komponenten

4

Edukt 3

HCID 6422Trifluoroacetic acidHCID 579405262-Chloro-9-cyclopentyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one3×HCID 178492706HCID 178492706, Verbindung2×

Produkt 1

HCID 178492710HCID 178492710, VerbindungAusbeute 40,6 %

Versuchsvorschrift

2-Chloro-9-cyclopentyl-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (Intermediate 1) (0.13 g, 0.43 mmol, 1 eq), 4-amino-N-(trans-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide (Intermediate 11) (0.26 g, 0.67 mmol, 1.5 eq) and TFA (0.17 mL, 2.2 mmol, 5 eq) in TFE (3 mL) were heated together at 80° C. for 18 hours. Further quantity of Intermediate 1 (0.10 g) was added and the reaction further heated for 48 hours. RM was concentrated in vacuo and the residue was purified by flash column chromatography on silica eluting with 0→20% ammonia/MeOH in DCM gradient followed by preparative HPLC (Preparative 4) then finally preparative RP-HPLC-MS (Preparative 1) to give 4-(9-cyclopentyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-((trans)-4-(4-(cyclopropylmethyl)piperazin-1-yl)cyclohexyl)-3-methoxybenzamide (0.11 g, 26%).

Aufarbeitung

  1. customthe reaction
  2. temperaturefurther heated for 48 hours
  3. concentrationRM was concentrated in vacuo
  4. customthe residue was purified by flash column chromatography on silica eluting with 0→20% ammonia/MeOH in DCM gradient

Quellen und Nachweise

ORD-Eintrag
ord-3b822e7895294bf19c3430a5e2f36cff
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133199B2

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