Propargyl alcohol → (E)-N-(diaminomethylene)-3-(3,5-difluoro-4-(4-(N-(2-(2-(2-(2-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethyl)sulfamoyl)phenoxy)phenyl)-2-methylacrylamide

HRID 45695Notes

Reaction equation

HRID 45695 reaction equation
[N:1]([CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][NH:15][S:16]([C:19]1[CH:42]=[CH:41][C:22]([O:23][C:24]2[C:29]([F:30])=[CH:28][C:27](/[CH:31]=[C:32](\[CH3:39])/[C:33]([N:35]=[C:36]([NH2:38])[NH2:37])=[O:34])=[CH:26][C:25]=2[F:40])=[CH:21][CH:20]=1)(=[O:18])=[O:17])=[N+:2]=[N-:3].[CH2:43]([OH:46])[C:44]#[CH:45].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>C(O)(C)(C)C.O.S([O-])([O-])(=O)=O.[Cu+2]>[NH2:37][C:36]([NH2:38])=[N:35][C:33](=[O:34])/[C:32](/[CH3:39])=[CH:31]/[C:27]1[CH:28]=[C:29]([F:30])[C:24]([O:23][C:22]2[CH:41]=[CH:42][C:19]([S:16](=[O:18])(=[O:17])[NH:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][CH2:8][CH2:7][O:6][CH2:5][CH2:4][N:1]3[CH:45]=[C:44]([CH2:43][OH:46])[N:3]=[N:2]3)=[CH:20][CH:21]=2)=[C:25]([F:40])[CH:26]=1

Participants

7

Reactant 3

HCID 7859Propargyl alcoholHCID 23667548Sodium AscorbateHCID 86672341(E)-3-(4-(4-(N-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)sulfamoyl)phenoxy)-3,5-difluorophenyl)-N-(diaminomethylene)-2-methylacrylamide

Product 1

HCID 70872283(E)-N-(diaminomethylene)-3-(3,5-difluoro-4-(4-(N-(2-(2-(2-(2-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethyl)sulfamoyl)phenoxy)phenyl)-2-methylacrylamideYield 30%

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

To a mixture of (E)-3-(4-(4-(N-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)sulfamoyl)phenoxy)-3,5-difluorophenyl)-N-(diaminomethylene)-2-methylacrylamide (70 mg, 0.11 mmol) and propargyl alcohol (6.4 mg. 0.11 mmol) in t-butanol (0.22 mL) and water (0.22 mL) was added 1 M sodium ascorbate (11 μL, 0.011 mmol) and 0.3 M copper sulfate (3.6 μL, 0.0011 mmol) and the reaction was stirred at RT. After 14 hours, the product was purified by preparative HPLC to give the title compound (22 mg) as a TFA salt. 1H-NMR (400 mHz, CD3OD) δ 7.93 (s, 1H), 7.84 (m, 2H), 7.44 (s, 1H), 7.30 (m, 2H), 7.11 (m, 2H), 4.64 (d, j=0.6 Hz, 2H), 4.55 (t, j=5.0 Hz, 2H), 3.86 (t, j=5.0 Hz, 2H), 3.57 (m, 4H), 3.52-3.42 (m, 6H), 3.03 (t, j=5.4 Hz, 2H), 2.18 (d, j=1.3 Hz, 3H). MS (m/z): 668.14 (M+H).

Workup

  1. customthe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-0d04e3ef2ee74886b47e11938b893e77
Source dataset
uspto-grants-2013_09
Patent number
US08541448B2

Reaction notes

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