Hydrazine → 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-1H-indazol-3-amine
Reaction equation
[NH2:1][C@@H:2]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=1)[CH2:3][NH:4][C:5]1[S:6][C:7]([C:10]2[CH:11]=[CH:12][C:13](F)=[C:14]([CH:17]=2)[C:15]#[N:16])=[CH:8][N:9]=1.[NH2:30][NH2:31]>>[NH2:1][C@@H:2]([CH2:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([F:28])([F:29])[F:27])=[CH:24][CH:25]=1)[CH2:3][NH:4][C:5]1[S:6][C:7]([C:10]2[CH:17]=[C:14]3[C:13](=[CH:12][CH:11]=2)[NH:31][N:30]=[C:15]3[NH2:16])=[CH:8][N:9]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrile (0.042 g, 0.100 mmol) was taken up in hydrazine (0.50 mL) in a microwave safe tube. The tube was sealed and heated in a Personal Chemistry microwave unit to 100° C. for 5 minutes. The hydrazine was then removed under reduced pressure, and the residue was purified by HPLC (95:5 to 70:30 water:MeCN over 45 minutes), affording 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-1H-indazol-3-amine (0.027 g, 0.062 mmol, 62% yield) as a yellow amorphous solid. 1H NMR (400 MHz, CD3OD) δ ppm 7.75-7.71 (m, 1H), 7.67-7.60 (m, 2H), 7.51-7.45 (m, 3H), 7.34-7.25 (m, 2H), 3.64-3.48 (m, 2H), 3.42-3.34 (m, 1H), 3.09-3.00 (m, 1H), 2.89 (dd, J=13.8, 7.1 Hz, 1H), 1.95-1.91 (m, 1H). HRMS (M+H) for C25H27F3N6O2S calc. 433.14168, obs. 433.14225.
Workup
- customThe tube was sealed
- customThe hydrazine was then removed under reduced pressure
- customthe residue was purified by HPLC (95:5 to 70:30 water:MeCN over 45 minutes)
Sources & evidence
- ORD record
- ord-03729cea78a64109a0201374506ab188
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08084479B2
Reaction notes
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