Ammonium Chloride → 4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-6-methoxybenzene-1,3-diamine

HRID 1842698

Reaktionsgleichung

Reaktionsgleichung von HRID 1842698
[CH3:1][N:2]1[CH2:6][C@@H:5]2[N:7]([C:10]3[C:15]([N+:16]([O-])=O)=[CH:14][C:13]([NH:19][C:20]4[N:25]=[C:24]([C:26]5[CH:27]=[N:28][N:29]6[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=56)[C:23]([Cl:35])=[CH:22][N:21]=4)=[C:12]([O:36][CH3:37])[CH:11]=3)[CH2:8][CH2:9][C@@H:4]2[CH2:3]1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[CH3:1][N:2]1[CH2:6][C@@H:5]2[N:7]([C:10]3[CH:11]=[C:12]([O:36][CH3:37])[C:13]([NH:19][C:20]4[N:25]=[C:24]([C:26]5[CH:27]=[N:28][N:29]6[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=56)[C:23]([Cl:35])=[CH:22][N:21]=4)=[CH:14][C:15]=3[NH2:16])[CH2:8][CH2:9][C@@H:4]2[CH2:3]1

Komponenten

6

Edukt 2

HCID 25517Ammonium ChlorideHCID 71270223N-[4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-2-methoxy-5-nitrophenyl]-5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2×

Produkt 1

HCID 866772374-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-6-methoxybenzene-1,3-diamineAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23925IronKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of N-[4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-2-methoxy-5-nitrophenyl]-5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 36, 155 mg, 0.30 mmol), iron (100 mg, 1.79 mmol) and NH4Cl (11.2 mg, 0.21 mmol) in ethanol (12 mL) and water (4 mL) was heated at reflux for 2 h. The mixture was then cooled and filtered though decalite (a type of diatomaceous earth) and the filtrate was concentrated in vacuo to provide a brown gum. Purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (105 mg, 72%) as a gum; 1H NMR: (CDCl3) 1.76-1.80 (1H, m), 2.03-2.20 (2H, m), 2.28 (3H, s), 2.48 (1H, dd), 2.59-2.63 (2H, m), 2.76-2.98 (2H, m), 3.46 (1H, dt), 3.78 (2H, s), 3.84 (3H, s), 4.07-4.10 (1H, m), 6.73 (1H, s), 6.94 (1H, td), 7.36 (1H, ddd), 7.51 (1H, s), 7.86 (1H, s), 8.35 (1H, s), 8.54 (1H, d), 8.65 (1H, d), 8.93 (1H, s); m/z: ES+ MH+ 491.29.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. temperatureThe mixture was then cooled
  4. filtrationfiltered though decalite (a type of diatomaceous earth) and the filtrate
  5. concentrationwas concentrated in vacuo
  6. customto provide a brown gum
  7. customPurification by FCC
  8. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-69c106480d7449baa1c8cdf706abab79
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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