Triacetoxyperiodinane → 5-(2-((2S,3S)-2-amino-4-hydroxy-3-(4-(trifluoromethyl)phenyl)pentylamino)thiazol-5-yl)indolin-2-one

HRID 661117Notes

Reaction equation

HRID 661117 reaction equation
Br[C:2]1[S:6][C:5]([N:7](C(OC(C)(C)C)=O)[CH2:8][C@@H:9]([NH:23]C(=O)OC(C)(C)C)[C@H:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[CH2:11][OH:12])=[N:4][CH:3]=1.[CH3:38]C(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.BrC1SC(N(C(OC(C)(C)C)=O)C[C@@H](NC(=O)OC(C)(C)C)[C@H](C2C=CC(C(F)(F)F)=CC=2)C=O)=NC=1.C[Mg]Br.BrC1SC(N(C(OC(C)(C)C)=O)C[C@@H](NC(=O)OC(C)(C)C)[C@H](C2C=CC(C(F)(F)F)=CC=2)[C@@H](O)C)=NC=1.CC1(C)C(C)(C)OB([C:146]2[CH:147]=[C:148]3[C:152](=[CH:153][CH:154]=2)[NH:151][C:150](=[O:155])[CH2:149]3)O1>>[NH2:23][C@@H:9]([C@H:10]([C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][CH:14]=1)[CH:11]([OH:12])[CH3:38])[CH2:8][NH:7][C:5]1[S:6][C:2]([C:146]2[CH:147]=[C:148]3[C:152](=[CH:153][CH:154]=2)[NH:151][C:150](=[O:155])[CH2:149]3)=[CH:3][N:4]=1

Participants

7

Reactant 6

HCID 159087TriacetoxyperiodinaneHCID 219314865-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-oneHCID 57634162(2S,3S)-3-(Boc)amino-4-(5-bromothiazol-2-yl(Boc)amino)-2-(4-(trifluoromethyl)phenyl)butan-1-ol2×HCID 86613778tert-butyl (2S,3S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-oxo-3-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamateHCID 86613779tert-butyl (2S,3S,4S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-hydroxy-3-(4-(trifluoromethyl)phenyl)pentan-2-ylcarbamateHCID 178418573HCID 178418573, compound

Product 1

HCID 576339805-(2-((2S,3S)-2-amino-4-hydroxy-3-(4-(trifluoromethyl)phenyl)pentylamino)thiazol-5-yl)indolin-2-one

Procedure

The title compound was synthesized in a manner similar to Example 158 starting with tert-butyl (2S,3S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-hydroxy-3-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate as shown in Scheme 36. After an oxidation with Dess-Martin periodinane, tert-butyl (2S,3S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-hydroxy-3-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate was converted to tert-butyl (2S,3S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-oxo-3-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate. The aldehyde tert-butyl (2S,3S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-oxo-3-(4-(trifluoromethyl)-phenyl)butan-2-ylcarbamate reacted with methylmagnesium bromide to generate tert-butyl (2S,3S,4S)-1-(5-bromothiazol-2-yl-(Boc)-amino)-4-hydroxy-3-(4-(trifluoromethyl)phenyl)pentan-2-ylcarbamate as the intermediate for the Suzuki reaction with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolin-2-one leading to the final product. MS m/z: 477 (M+1). 1H NMR (400 MHz, CD3OD) δ ppm 7.68 (d, J=8.22 Hz, 2H) 7.54 (d, J=8.22 Hz, 2H) 7.34 (d, J=1.56 Hz, 1H) 7.26 (dd, J=8.12, 1.86 Hz, 1H) 6.87 (d, J=8.22 Hz, 1H) 4.39 (dd, J=9.00, 6.06 Hz, 1H) 3.77-3.82 (m, 1H) 3.41 (dd, J=13.69, 5.28 Hz, 1H) 3.37 (s, 3H) 3.20 (dd, J=13.50, 8.02 Hz, 1H) 2.92 (dd, J=9.00, 3.52 Hz, 1H) 1.08 (d, J=6.26 Hz, 3H).

Sources & evidence

ORD record
ord-b25e72845ae041b98b939d0024004782
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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