Hydrochloric Acid → tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-((2-(4-isopropoxyphenyl)-6-(pyrazin-2-yl)pyridin-4-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 523196Notes

Reaction equation

HRID 523196 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:18]2[CH:23]=[N:22][CH:21]=[CH:20][N:19]=2)[CH:3]=1.[OH:24][C@H:25]1[CH2:65][N:28]2[C:29](=[O:64])[C@@H:30]([NH:56][C:57](=[O:63])[O:58][C:59]([CH3:62])([CH3:61])[CH3:60])[C@H:31]([CH3:55])[CH2:32][CH:33]([CH3:54])[CH2:34][CH2:35][CH:36]=[CH:37][C@@H:38]3[CH2:43][C@@:39]3([C:44](=[O:53])[NH:45][S:46]([C:49]3([CH3:52])[CH2:51][CH2:50]3)(=[O:48])=[O:47])[NH:40][C:41](=[O:42])[C@@H:27]2[CH2:26]1.CC(C)([O-])C.[K+].Cl>CS(C)=O>[CH:15]([O:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:7]=[C:2]([O:24][C@H:25]3[CH2:65][N:28]4[C:29](=[O:64])[C@@H:30]([NH:56][C:57](=[O:63])[O:58][C:59]([CH3:62])([CH3:61])[CH3:60])[C@H:31]([CH3:55])[CH2:32][CH:33]([CH3:54])[CH2:34][CH2:35][CH:36]=[CH:37][C@@H:38]5[CH2:43][C@@:39]5([C:44](=[O:53])[NH:45][S:46]([C:49]5([CH3:52])[CH2:51][CH2:50]5)(=[O:47])=[O:48])[NH:40][C:41](=[O:42])[C@@H:27]4[CH2:26]3)[CH:3]=[C:4]([C:18]3[CH:23]=[N:22][CH:21]=[CH:20][N:19]=3)[N:5]=2)=[CH:9][CH:10]=1)([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 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)carbamateHCID 901182852-(4-Chloro-6-(4-isopropoxyphenyl)pyridin-2-yl)pyrazine

Product 1

HCID 118520718tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-((2-(4-isopropoxyphenyl)-6-(pyrazin-2-yl)pyridin-4-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 dry 2 dram vial equipped with a stir bar and charged with 2-(4-chloro-6-(4-isopropoxyphenyl)pyridin-2-yl)pyrazine (37 mg, 0.11 mmol) was added 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 (46 mg, 0.076 mmol). To the vial was added DMSO (1.25 mL). The mixture was stirred for 2 minutes to afford a red, homogeneous solution. To the solution was added potassium tert-butoxide (43 mg, 0.38 mmol) to afford a very deep amber solution. The solution was stirred at room temperature for 2 h. To the solution was added aq. 1M HCl (3 mL) upon which a solid precipitated. The mixture was transfered to a 125 mL reparatory funnel and was diluted with water:brine (20 mL:20 mL). The mixture was extracted with EtOAc (2×30 mL). The combined organics were dried over MgSO4; filtered; then concentrated in vacuo to afford tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-2-((2-(4-isopropoxyphenyl)-6-(pyrazin-2-yl)pyridin-4-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 as a solid residue. MS: MS m/z 900.6 (M++1).

Workup

  1. customTo a dry 2 dram vial equipped with a stir bar
  2. customto afford a red, homogeneous solution
  3. customto afford a very deep amber solution
  4. stirringThe solution was stirred at room temperature for 2 h
  5. customprecipitated
  6. customThe mixture was transfered to a 125 mL reparatory funnel
  7. additionwas diluted with water
  8. extractionThe mixture was extracted with EtOAc (2×30 mL)
  9. dry with materialThe combined organics were dried over MgSO4
  10. filtrationfiltered
  11. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-4b21a1d6c1b9470cbeae6c05c89775db
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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