Potassium tert-butoxide → tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-((3-(dimethylamino)-6-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-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

HRID 1852127Notes

Reaction equation

HRID 1852127 reaction equation
[OH:1][C@H:2]1[CH2:42][N:5]2[C:6](=[O:41])[C@@H:7]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C@H:8]([CH3:32])[CH2:9][CH:10]([CH3:31])[CH2:11][CH2:12][CH:13]=[CH:14][C@@H:15]3[CH2:20][C@@:16]3([C:21](=[O:30])[NH:22][S:23]([C:26]3([CH3:29])[CH2:28][CH2:27]3)(=[O:25])=[O:24])[NH:17][C:18](=[O:19])[C@@H:4]2[CH2:3]1.Cl[C:44]1[C:53]2[C:48](=[CH:49][C:50]([O:54][CH3:55])=[CH:51][CH:52]=2)[CH:47]=[C:46]([N:56]([CH3:58])[CH3:57])[N:45]=1.CC(C)([O-])C.[K+]>CS(C)=O>[CH3:57][N:56]([CH3:58])[C:46]1[N:45]=[C:44]([O:1][C@H:2]2[CH2:42][N:5]3[C:6](=[O:41])[C@@H:7]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C@H:8]([CH3:32])[CH2:9][CH:10]([CH3:31])[CH2:11][CH2:12][CH:13]=[CH:14][C@@H:15]4[CH2:20][C@@:16]4([C:21](=[O:30])[NH:22][S:23]([C:26]4([CH3:29])[CH2:28][CH2:27]4)(=[O:24])=[O:25])[NH:17][C:18](=[O:19])[C@@H:4]3[CH2:3]2)[C:53]2[C:48]([CH:47]=1)=[CH:49][C:50]([O:54][CH3:55])=[CH:51][CH:52]=2

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 594234521-chloro-6-methoxy-N,N-dimethylisoquinolin-3-amineHCID 71004914tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-hydroxy-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-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 86683201tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-((3-(dimethylamino)-6-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-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

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-hydroxy-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-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, 0.246 mmol),1-chloro-6-methoxy-N,N-dimethylisoquinolin-3-amine (69.8 mg, 0.295 mmol), and potassium tert-butoxide (138 mg, 1.228 mmol) was added DMSO (5 mL) and then the mixture was sonicated for 15 min. The resulting solution was stirred for 4 h at room temperature. The reaction was quenched with water, acidified with 6 N HCl to pH=4, and extracted with EtOAc. The organic layer was collected, washed with brine, dried over MgSO4, filtered, and concentrated to give the crude tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-((3-(dimethylamino)-6-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-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 that was used in the next step as is. MS: MS m/z 811.6 (M++1).

Workup

  1. customthe mixture was sonicated for 15 min
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. customThe organic layer was collected
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1589d6fbbd4346e9aee70d6081347939
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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