1,1'-Carbonyldiimidazole → N-[17-(3-chloro-6-methoxyisoquinolin-1-yloxy)-13-methyl-2,14-dioxo-3,13,15-triaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl) sulfonamide

HRID 905542Notes

Reaction equation

HRID 905542 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([O:14][CH:15]2[CH2:32][CH:31]3[N:17]([C:18](=[O:38])[N:19]([CH3:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH:25][CH:26]4[C:28]([C:34]([OH:36])=O)([NH:29][C:30]3=[O:33])[CH2:27]4)[CH2:16]2)[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][CH:6]=2.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:51]1([S:54]([NH2:57])(=[O:56])=[O:55])[CH2:53][CH2:52]1.C1CCN2C(=NCCC2)CC1>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([O:14][CH:15]2[CH2:32][CH:31]3[N:17]([C:18](=[O:38])[N:19]([CH3:37])[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH:25][CH:26]4[C:28]([C:34]([NH:57][S:54]([CH:51]5[CH2:53][CH2:52]5)(=[O:56])=[O:55])=[O:36])([NH:29][C:30]3=[O:33])[CH2:27]4)[CH2:16]2)[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][CH:6]=2

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 76674825HCID 76674825, compound

Product 1

HCID 76674828N-[17-(3-chloro-6-methoxyisoquinolin-1-yloxy)-13-methyl-2,14-dioxo-3,13,15-triaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl) sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 17-(3-chloro-6-methoxyisoquinolin-1-yloxy)-13-methyl-2,14-dioxo-3,13,15-triaza-tricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid (42), (80 mg, 0.147 mmol) and carbonyldiimidazol (48 mg, 0.295 mmol) in dry THF (25 mL) was stirred at reflux under nitrogen for 3 h. Then, the reaction mixture was cooled down to room temperature and cyclopropylsulfonamide (54 mg, 0.442 mmol) and DBU (52 mg, 0.34 mmol) were added. The resulting solution was stirred at 50° C. for 48 h. Then, the reaction mixture was partitioned between AcOEt ethyl acetate and water. The organic layer was dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel (CH2Cl2/EtOAc, 95:05) to give the title product contaminated with cyclopropylsulfonamide. This solid was triturated 10 min in water and filtered, washed with water, dried under high vacuum, triturated again in diethylether and filtered to give 37 mg (39%) of the title product 43 as a white powder: m/z=647 (M+H)+; 1H-NMR (CDCl3): 10.40 (br s, 1H), 7.95 (d, J=9.1 Hz, 1H), 7.55 (s, 1H), 7.15 (s, 1H), 7.10 (dd, J=9.12 Hz, 2.4 Hz, 1H), 6.90 (d, J=2.4 Hz, 1H), 5.85 (br s, 1H), 5.65 (dd, J=18.2 Hz, 8.0 Hz, 1H), 5.15 (t, J=10.0 Hz, 1H), 4.8 (t, J=7.2 Hz, 1H), 4.10 (dd, J=11.3 Hz, 3.8 Hz, 1H), 3.9 (s, 3H), 3.60-3.70 (m, 1H), 3.6 (d, J=11.3 Hz, 1H), 3.10-3.20 (m, 1H), 2.90-3.00 (m, 1H), 2.85 (s, 3H), 2.4-2.6 (m, 3H), 1.90-2.20 (m, 3H), 1.25-1.60 (m, 7H), 0.90-1.10 (m, 2H).

Workup

  1. temperatureat reflux under nitrogen for 3 h
  2. customThen, the reaction mixture was partitioned between AcOEt ethyl acetate and water
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica gel (CH2Cl2/EtOAc, 95:05)

Sources & evidence

ORD record
ord-5793b2e7005d40eaa39161b87cc33511
Source dataset
uspto-grants-2011_09
Patent number
US08012939B2

Reaction notes

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