Dichloromethane → (2R,6S,7R,13aS,14aR,16aS,Z)-6-amino-2-((2-(4-isopropoxyphenyl)-6-(pyrazin-2-yl)pyridin-4-yl)oxy)-7,9-dimethyl-N-((1-methylcyclopropyl)sulfonyl)-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]diazacyclopentadecine-14a-carboxamide trifluoroacetic acid salt

HRID 523197Notes

Reaction equation

HRID 523197 reaction equation
[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[C:15]([O:17][C@H:18]3[CH2:58][N:21]4[C:22](=[O:57])[C@@H:23]([NH:49]C(=O)OC(C)(C)C)[C@H:24]([CH3:48])[CH2:25][CH:26]([CH3:47])[CH2:27][CH2:28][CH:29]=[CH:30][C@@H:31]5[CH2:36][C@@:32]5([C:37](=[O:46])[NH:38][S:39]([C:42]5([CH3:45])[CH2:44][CH2:43]5)(=[O:41])=[O:40])[NH:33][C:34](=[O:35])[C@@H:20]4[CH2:19]3)[CH:14]=[C:13]([C:59]3[CH:64]=[N:63][CH:62]=[CH:61][N:60]=3)[N:12]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].C(Cl)Cl.[F:68][C:69]([F:74])([F:73])[C:70]([OH:72])=[O:71]>C1(C)C=CC=CC=1>[F:68][C:69]([F:74])([F:73])[C:70]([OH:72])=[O:71].[NH2:49][C@@H:23]1[C:22](=[O:57])[N:21]2[CH2:58][C@H:18]([O:17][C:15]3[CH:14]=[C:13]([C:59]4[CH:64]=[N:63][CH:62]=[CH:61][N:60]=4)[N:12]=[C:11]([C:8]4[CH:9]=[CH:10][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:6][CH:7]=4)[CH:16]=3)[CH2:19][C@H:20]2[C:34](=[O:35])[NH:33][C@:32]2([C:37]([NH:38][S:39]([C:42]3([CH3:45])[CH2:44][CH2:43]3)(=[O:40])=[O:41])=[O:46])[CH2:36][C@H:31]2[CH:30]=[CH:29][CH2:28][CH2:27][CH:26]([CH3:47])[CH2:25][C@H:24]1[CH3:48]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 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)carbamate2×

Product 1

HCID 118512239(2R,6S,7R,13aS,14aR,16aS,Z)-6-amino-2-((2-(4-isopropoxyphenyl)-6-(pyrazin-2-yl)pyridin-4-yl)oxy)-7,9-dimethyl-N-((1-methylcyclopropyl)sulfonyl)-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]diazacyclopentadecine-14a-carboxamide trifluoroacetic acid salt

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a 25 mL round-bottom flask equipped with a stir bar and charged with 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 (all material from Step 1) was added CH2Cl2 (1 mL), then trifluoroacetic acid (1.0 mL, 13 mmol). The solution was stirred at room temperature for 2 h. The reaction solution was diluted with toluene (2 mL) and then concentrated in vacuo to afford (2R,6S,7R,13aS,14aR,16aS,Z)-6-amino-2-((2-(4-isopropoxyphenyl)-6-(pyrazin-2-yl)pyridin-4-yl)oxy)-7,9-dimethyl-N-((1-methylcyclopropyl)sulfonyl)-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]diazacyclopentadecine-14a-carboxamide trifluoroacetic acid salt as an amber solid residue. MS: MS m/z 800.5 (M++1).

Workup

  1. customTo a 25 mL round-bottom flask equipped with a stir bar
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-68b2f8d8a604481f9df474f2584f67a1
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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