Hydrochloric Acid → HCID 15947223, compound

HRID 1008973Notes

Reaction equation

[CH:1]1([C:7]2[C:8]3[S:28][C:27]([C:29]([O:31]C)=[O:30])=[CH:26][C:9]=3[N:10]3[C:16]=2[C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=2[N:13]([CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])[CH2:12][CH2:11]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[K+].Cl>O1CCOCC1>[CH:1]1([C:7]2[C:8]3[S:28][C:27]([C:29]([OH:31])=[O:30])=[CH:26][C:9]=3[N:10]3[C:16]=2[C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=2[N:13]([CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])[CH2:12][CH2:11]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution (0.05 M) of methyl 12-cyclohexyl-5-[2-(dimethylamino)ethyl]-6,7-dihydro-5H-thieno[2′,3′:4,5]pyrrolo[1,2-d][1,4]benzodiazepine-10-carboxylate (from Step 1) in dioxane was treated with 1 N KOH solution (5 eq.). The mixture was stirred at 60° C. for 2 h then treated with 1 N hydrochloric acid. The solvents were removed in vacuo and the residue purified by RP-HPLC (column: Waters XTERRA PREP MS C18, 5 μm; solvents: A: water+0.1% trifluoroacetic acid; B: MeCN+0.1% trifluoroacetic acid; 10% B in A isocratic for 1 min, linear to 50% A in B in 4 min, linear to 40% A in B in 1 min, 40% A in B isocratic for 1 min, linear to 30% A in B in 1 min) to afford the title compound (59% over two steps) after lyophilisation as a solid. 1H-NMR (400 MHz DMSO-d6, 300K δ) 9.12 (bs, 1H), 7.93 (s, 1H), 7.48-7.23 (m, 4H), 4.18 (m, 2H), 3.46 (m, 4H), 3.13 (m, 2H), 2.67 (m, 1H), 1.78-1.27 (m, 10H). MS (ES+) m/z: 438 [M+H]+.

Workup

customThe solvents were removed in vacuo
customthe residue purified by RP-HPLC (column
wait10% B in A isocratic for 1 min
waitlinear to 50% A in B in 4 min
waitlinear to 40% A in B in 1 min
wait40% A in B isocratic for 1 min

Sources & evidence

ORD record: ord-1e9163c263384ef4a837738ffc426647
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07973026B2

Reaction notes

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