Hydrochloric Acid → N-[(1R,2R)-2-[[5-chloro-2-[[7-methoxy-3-(2-methoxyethyl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]amino]pyrimidin-4-yl]amino]cyclohexyl]methanesulfonamide

HRID 1040645Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1040645
[CH3:1][O:2][C:3]1[C:4]([NH2:18])=[CH:5][C:6]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][O:15][CH3:16])[CH2:9][CH2:8][C:7]=2[CH:17]=1.Cl[C:20]1[N:25]=[C:24]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]2[NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[C:23]([Cl:38])=[CH:22][N:21]=1.Cl.C(O)(C)C.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>O1CCOCC1>[Cl:38][C:23]1[C:24]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]2[NH:33][S:34]([CH3:37])(=[O:36])=[O:35])=[N:25][C:20]([NH:18][C:4]2[C:3]([O:2][CH3:1])=[CH:17][C:7]3[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][O:15][CH3:16])[CH2:11][CH2:12][C:6]=3[CH:5]=2)=[N:21][CH:22]=1

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 574161508-Methoxy-3-(2-methoxyethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-amineHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Produkt 1

HCID 53482132N-[(1R,2R)-2-[[5-chloro-2-[[7-methoxy-3-(2-methoxyethyl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]amino]pyrimidin-4-yl]amino]cyclohexyl]methanesulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

8-Methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (165 mg, 0.000659 mol), N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (220 mg, 0.00066 mol), 4 M of Hydrogen chloride in 1,4-Dioxane (200 uL) and Isopropyl alcohol (6.6 mL, 0.086 mol;) were combined in a microwave vessel. Heat at 130° C. for 20 min. The mixture was treated with 500 mgs of MP-carbonate resin and stirred for 20 min. The mixture was filtered and concentrated and put on high vac overnight. The crude solid was dissolved in DCM and purified on an ISCO column (40 g, SiO2, 100% DCM to MeOH/DCM gradient) to afford N-((1R,2R)-2-{5-Chloro-2-[8-methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonam (99 mg, 48%). MP: 92-94° C. 1H-NMR (CDCl3, 400 MHz): 1H-NMR (CDCL3) δ 7.96 (s, 1H), 7.32 (s, 1H), 6.67 (s, 1H), 5.37-5.31 (m, 2H), 3.99-3.95 (broad m, 1H), 3.88 (s, 1H), 3.56 (br s, 2H), 3.38 (s, 1H), 3.28-3.24 (m, 1H), 2.99-2.70 (complex series of m, 11H), 2.26-2.20 (m, 2H), 1.88-1.80 (m, 2H), 1.41-1.28 (m, 6H), 0.92-0.85 (m, 2H); LC/MS: 552.92 (M+H).

Aufarbeitung

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. waitput on high vac overnight
  4. dissolutionThe crude solid was dissolved in DCM
  5. custompurified on an ISCO column (40 g, SiO2, 100% DCM to MeOH/DCM gradient)
  6. customto afford N-((1R,2R)-2-{5-Chloro-2-[8-methoxy-3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonam (99 mg, 48%)

Quellen und Nachweise

ORD-Eintrag
ord-d1432202d6b34a168c28b5b226703b0b
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08552186B2

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