Potassium tert-butoxide → tert-butyl (2R,6S,7R,13aS,14aR,16aS,Z)-14a-(1-(fluoromethyl)cyclopropylsulfonylcarbamoyl)-2-(2-(4-isopropoxyphenyl)-7-methoxyquinolin-4-yloxy)-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-ylcarbamate

HRID 1852195Notes

Reaction equation

HRID 1852195 reaction equation
[F:1][CH2:2][C:3]1([S:6]([NH:9][C:10]([C@@:12]23[CH2:27][C@H:26]2[CH:25]=[CH:24][CH2:23][CH2:22][CH:21]([CH3:28])[CH2:20][C@@H:19]([CH3:29])[C@H:18]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[C:17](=[O:38])[N:16]2[CH2:39][C@H:40]([OH:42])[CH2:41][C@H:15]2[C:14](=[O:43])[NH:13]3)=[O:11])(=[O:8])=[O:7])[CH2:5][CH2:4]1.Cl[C:45]1[C:54]2[C:49](=[CH:50][C:51]([O:55][CH3:56])=[CH:52][CH:53]=2)[N:48]=[C:47]([C:57]2[CH:62]=[CH:61][C:60]([O:63][CH:64]([CH3:66])[CH3:65])=[CH:59][CH:58]=2)[CH:46]=1.CC([O-])(C)C.[K+]>CS(C)=O>[F:1][CH2:2][C:3]1([S:6]([NH:9][C:10]([C@@:12]23[CH2:27][C@H:26]2[CH:25]=[CH:24][CH2:23][CH2:22][CH:21]([CH3:28])[CH2:20][C@@H:19]([CH3:29])[C@H:18]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:34])[CH3:35])[C:17](=[O:38])[N:16]2[CH2:39][C@H:40]([O:42][C:45]4[C:54]5[C:49](=[CH:50][C:51]([O:55][CH3:56])=[CH:52][CH:53]=5)[N:48]=[C:47]([C:57]5[CH:62]=[CH:61][C:60]([O:63][CH:64]([CH3:66])[CH3:65])=[CH:59][CH:58]=5)[CH:46]=4)[CH2:41][C@H:15]2[C:14](=[O:43])[NH:13]3)=[O:11])(=[O:7])=[O:8])[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 709782674-Chloro-2-(4-isopropoxyphenyl)-7-methoxyquinolineHCID 71005415tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-14a-(((1-(fluoromethyl)cyclopropyl)sulfonyl)carbamoyl)-2-hydroxy-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate

Product 1

HCID 86683252tert-butyl (2R,6S,7R,13aS,14aR,16aS,Z)-14a-(1-(fluoromethyl)cyclopropylsulfonylcarbamoyl)-2-(2-(4-isopropoxyphenyl)-7-methoxyquinolin-4-yloxy)-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-ylcarbamateYield 60%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-14a-(((1-(fluoromethyl)cyclopropyl)sulfonyl)carbamoyl)-2-hydroxy-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate (150 mg, 0.238 mmole) and 4-chloro-2-(4-isopropoxyphenyl)-7-methoxyquinoline (93 mg, 0.284 mmole) in DMSO (8 mL) was added t-BuOK (133 mg, 1.19 mmol, 1 M solution in THF, 1.2 mL) at room temperature under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 h. The reaction mass was quenched with aqueous citric acid solution and extracted with ethyl acetate (10 mL×2). The combined organic layer was washed with water, brine solution, dried over anhydrous Na2SO4 and evaporated under reduced pressure to get crude compound. The crude compound was purified by HPLC to get 130 mg (60%) of desired compound tert-butyl (2R,6S,7R,13aS,14aR,16aS,Z)-14a-(1-(fluoromethyl)cyclopropylsulfonylcarbamoyl)-2-(2-(4-isopropoxyphenyl)-7-methoxyquinolin-4-yloxy)-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-ylcarbamate as white solid. MS: MS m/z 921.5 (M++1).

Workup

  1. customThe reaction mass was quenched with aqueous citric acid solution
  2. extractionextracted with ethyl acetate (10 mL×2)
  3. washThe combined organic layer was washed with water, brine solution
  4. dry with materialdried over anhydrous Na2SO4
  5. customevaporated under reduced pressure
  6. customto get crude compound
  7. customThe crude compound was purified by HPLC

Sources & evidence

ORD record
ord-97fc9e4678794c3a83f96851de6ee910
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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