Trifluoroacetic acid methylene chloride → N-((S)-2-amino-3-(1H-indol-3-yl)propyl)-4-(2-aminoethyl)-3-(isoquinolin-6-yl)isoxazol-5-amine

HRID 598861Notes

Reaction equation

HRID 598861 reaction equation
[NH2:1][C@@H:2]([CH2:30][C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:33][CH:32]=1)[CH2:3][NH:4][C:5]1[O:9][N:8]=[C:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[N:15][CH:14]=[CH:13]3)[C:6]=1[CH2:20][CH2:21][NH:22]C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[NH2:1][C@@H:2]([CH2:30][C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:33][CH:32]=1)[CH2:3][NH:4][C:5]1[O:9][N:8]=[C:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[CH:16]=[N:15][CH:14]=[CH:13]3)[C:6]=1[CH2:20][CH2:21][NH2:22]

Participants

3

Reactant 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 57950676tert-Butyl 2-(5-((S)-2-amino-3-(1H-indol-3-yl)propylamino)-3-(isoquinolin-6-yl)isoxazol-4-yl)ethylcarbamate

Product 1

HCID 57950588N-((S)-2-amino-3-(1H-indol-3-yl)propyl)-4-(2-aminoethyl)-3-(isoquinolin-6-yl)isoxazol-5-amineYield 79%

Procedure

To a 25 mL of round-bottom flask was added tert-butyl 2-(5-((S)-2-amino-3-(1H-indol-3-yl)propylamino)-3-(isoquinolin-6-yl)isoxazol-4-yl)ethylcarbamate (11 mg, 21 μmol). 2 mL of 50% TFA/DCM was added to the reaction mixture dropwise. After 10 minutes, LC-MS showed that the BOC group had been removed. The reaction mixture was concentrated under reduced pressure and purified by preparative LC to give N-((S)-2-amino-3-(1H-indol-3-yl)propyl)-4-(2-aminoethyl)-3-(isoquinolin-6-yl)isoxazol-5-amine (7 mg, 79% yield). MS m/z: 427 (M+1); 1H NMR (400 MHz, CD3OD) δ ppm 9.79 (s, 1H), 8.56-8.66 (m, 2H), 8.52 (s, 1H), 8.45 (s, 1H), 8.18 (d, J=8.22 Hz, 1H), 7.60 (d, J=7.83 Hz, 1H), 7.39 (d, J=8.02 Hz, 1H), 7.26 (s, 1H), 7.14 (t, J=7.53 Hz, 1H), 7.06 (t, J=7.43 Hz, 1H), 3.75-3.79 (m, 2H), 3.62-3.71 (m, 1H), 3.20 (td, J=14.48, 7.04 Hz, 2H), 2.99 (s, 2H), 2.88 (d, J=6.46 Hz, 2H).

Workup

  1. customhad been removed
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. custompurified by preparative LC

Sources & evidence

ORD record
ord-6d7678eaf3614895b3e497879b6ddeb5
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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