Trifluoroacetic acid → (2R,6S,7R,13aS,14aR,16aS,Z)-6-amino-2-((3-(dimethylamino)-6-methoxyisoquinolin-1-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 TFA

HRID 1852128Notes

Reaction equation

HRID 1852128 reaction equation
[CH3:1][N:2]([CH3:57])[C:3]1[N:4]=[C:5]([O:15][C@H:16]2[CH2:56][N:19]3[C:20](=[O:55])[C@@H:21]([NH:47]C(=O)OC(C)(C)C)[C@H:22]([CH3:46])[CH2:23][CH:24]([CH3:45])[CH2:25][CH2:26][CH:27]=[CH:28][C@@H:29]4[CH2:34][C@@:30]4([C:35](=[O:44])[NH:36][S:37]([C:40]4([CH3:43])[CH2:42][CH2:41]4)(=[O:39])=[O:38])[NH:31][C:32](=[O:33])[C@@H:18]3[CH2:17]2)[C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2.[F:58][C:59]([F:64])([F:63])[C:60]([OH:62])=[O:61]>C(Cl)Cl>[OH:62][C:60]([C:59]([F:64])([F:63])[F:58])=[O:61].[NH2:47][C@@H:21]1[C:20](=[O:55])[N:19]2[CH2:56][C@H:16]([O:15][C:5]3[C:6]4[C:11](=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=4)[CH:12]=[C:3]([N:2]([CH3:1])[CH3:57])[N:4]=3)[CH2:17][C@H:18]2[C:32](=[O:33])[NH:31][C@:30]2([C:35]([NH:36][S:37]([C:40]3([CH3:43])[CH2:41][CH2:42]3)(=[O:38])=[O:39])=[O:44])[CH2:34][C@H:29]2[CH:28]=[CH:27][CH2:26][CH2:25][CH:24]([CH3:45])[CH2:23][C@H:22]1[CH3:46]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 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

Product 1

HCID 86683202(2R,6S,7R,13aS,14aR,16aS,Z)-6-amino-2-((3-(dimethylamino)-6-methoxyisoquinolin-1-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 TFAYield 99.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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 (50 mg, 0.062 mmol) was dissolved in DCM (4 mL) and trifluoroacetic acid (TFA, 1 ml, 12.98 mmol) was added. The reaction was stirred for 1 h at room temperature. The volatiles were removed under vacuum to give (2R,6S,7R,13aS,14aR,16aS,Z)-6-amino-2-((3-(dimethylamino)-6-methoxyisoquinolin-1-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 TFA (51 mg) which was used in the next step as is. MS: MS m/z 711.1 (M++1).

Workup

  1. customThe volatiles were removed under vacuum

Sources & evidence

ORD record
ord-4722c9debb4c4fab881de485929d67d4
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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