Cyclopropylamine → tert-Butyl (2-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl(2-methoxyethyl)carbamate

HRID 409978Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 409978
[C:1]([O:5][C:6](=[O:37])[N:7]([CH2:12][C:13]1[N:17]([CH3:18])[C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][C:30]=3[F:36])[CH:20]=2)=[N:15][CH:14]=1)[CH2:8][CH2:9][O:10][CH3:11])([CH3:4])([CH3:3])[CH3:2].ClC(Cl)(O[C:42](=[O:48])OC(Cl)(Cl)Cl)Cl.CC[N:52]([CH:56]([CH3:58])[CH3:57])C(C)C.C1(N)CC1>>[C:1]([O:5][C:6](=[O:37])[N:7]([CH2:12][C:13]1[N:17]([CH3:18])[C:16]([C:19]2[S:27][C:26]3[C:21](=[N:22][CH:23]=[CH:24][C:25]=3[O:28][C:29]3[CH:34]=[CH:33][C:32]([NH:35][C:42]([NH:52][CH:56]4[CH2:58][CH2:57]4)=[O:48])=[CH:31][C:30]=3[F:36])[CH:20]=2)=[N:15][CH:14]=1)[CH2:8][CH2:9][O:10][CH3:11])([CH3:4])([CH3:2])[CH3:3]

Komponenten

5

Edukt 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 57919490tert-Butyl (2-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl(2-methoxyethyl)carbamate

Produkt 1

HCID 58236627tert-Butyl (2-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl(2-methoxyethyl)carbamateAusbeute 92 %

Versuchsvorschrift

To a solution of the aniline 46 (400 mg, 0.758 mmol) was added triphosgene (1125 mg, 5 eq, 3.79 mmol) and iPr2NEt (490 mg, 5 eq, 3.79 mmol) and the reaction mixture was stirred at RT for an hour. Cyclopropylamine (6103 mg, 141 eq, 107 mmol) was added and the reaction mixture was stirred at RT overnight. The mixture was concentrated then diluted with DCM and washed with water. The organic phase was collected, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography (eluent 20% MeOH in EtOAc) to afford the desired compound 347 as a yellow oil (426 mg, 92% yield). MS (m/z)=611.4 (M+H).

Aufarbeitung

  1. stirringthe reaction mixture was stirred at RT overnight
  2. concentrationThe mixture was concentrated
  3. additionthen diluted with DCM
  4. washwashed with water
  5. customThe organic phase was collected
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography (eluent 20% MeOH in EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-f5c7734fe60345608b4dd09c5228b7c5
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759522B2

Notizen zur Reaktion

Wird geladen…