Hydrochloric Acid → HCID 178461765, compound

HRID 1670649Notes

Reaction equation

HRID 1670649 reaction equation
Cl.[F:2][C:3]1[CH:4]=[CH:5][C:6]2=[C:7]([CH:40]=1)[O:8][CH2:9][C:10]1[C:38]([F:39])=[CH:37][CH:36]=[CH:35][C:11]=1/[C:12]/2=[CH:13]\[C:14]1[CH:34]=[CH:33][C:17]2[N:18]([C@H:24]([CH3:32])[CH2:25][N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)/[C:19](=[N:21]/[C:22]#[N:23])/[NH:20][C:16]=2[CH:15]=1.[O:41]1CCOCC1>>[F:2][C:3]1[CH:4]=[CH:5][C:6]2=[C:7]([CH:40]=1)[O:8][CH2:9][C:10]1[C:38]([F:39])=[CH:37][CH:36]=[CH:35][C:11]=1/[C:12]/2=[CH:13]\[C:14]1[CH:34]=[CH:33][C:17]2[N:18]([C@H:24]([CH3:32])[CH2:25][N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)/[C:19](=[N:21]/[C:22]([NH2:23])=[O:41])/[NH:20][C:16]=2[CH:15]=1

Participants

4

Reactant 3

HCID 313Hydrochloric Acid2×HCID 312751,4-Dioxane2×HCID 178461764HCID 178461764, compound

Product 1

HCID 178461765HCID 178461765, compoundYield 38%

Procedure

Prepare a solution of 4 M hydrogen chloride in dioxane by diluting 12 M hydrochloric acid (10 mL) with dioxane (20 mL). Slowly add this solution to (E)-N—((R)-5-((E)-3,7-difluoro-6H-dibenzo[b,e]oxepin-11-ylidenemethyl)-1-(1-methyl-2-morpholin-4-yl-ethyl)-1,3-dihydro-benzoimidazol-2-ylidene)-cyanamide (0.005 mol, 3.0 g) at room temperature and stir for 48 hours. Quench the reaction mixture with aqueous 4 N potassium hydroxide solution, extract with dichloromethane and wash with saturated sodium bicarbonate solution. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate under reduce pressure. Purify on silica gel column using 1% methanol in dichloromethane to obtain the title compound (1.2 g, 38%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) mixture of (E,Z)-N isomers. Major isomer: δ 1.44 (d, 3H), 2.23-2.26 (m, 2H), 2.32-2.33 (m 1H), 2.63 (dd, 1H), 2.77-2.82 (m 1H), 3.29-3.46 (m, 5H), 4.77-4.82 (m, 1H), 5.35-5.44 (br d, 2H), 6.65 (dd, 1H), 6.89 (dt, 3H), 7.13 (s 1H), 7.1 (s, 1H), 7.21-7.28 (m, 2H), 7.31-7.42 (m 1H), 7.55-7.62 (m, 1H), 9.95 (s, 1H). Minor isomer: δ 1.39 (d, 3H, E,Z-isomer), 2.23-2.26 (m, 2H), 2.32-2.33 (m 2H), 2.88-3.0 (m 1H), 3.29-3.46 (m, 5H), 4.80-4.99 (m, 1H), 5.35-5.44 (br d, 2H), 6.65 (dd, 1H), 6.89 (dt, 3H), 7.13 (s 1H), 7.1 (s, 1H), 7.21-7.28 (m, 2H), 7.31-7.42 (m 1H), 7.55-7.62 (m, 1H), 9.95 (s, 1H).

Workup

  1. customQuench the reaction mixture with aqueous 4 N potassium hydroxide solution
  2. extractionextract with dichloromethane
  3. washwash with saturated sodium bicarbonate solution
  4. dry with materialDry the organic layer over anhydrous sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify on silica gel column

Sources & evidence

ORD record
ord-1cfa6dc50d9f41e8a52507fab4e0eabc
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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