Methanol → 2-Amino-2-((4-(5-(6-propylpyridin-3-yl)-1,2,4-oxadiazol-3-yl)indolin-1-yl)methyl)propane-1,3-diol

HRID 710476Notes

Reaction equation

HRID 710476 reaction equation
CC1(C)[O:7][CH2:6][C:5]([NH:32]C(=O)OC(C)(C)C)([CH2:8][N:9]2[C:17]3[C:12](=[C:13]([C:18]4[N:22]=[C:21]([C:23]5[CH:24]=[N:25][C:26]([CH2:29][CH2:30][CH3:31])=[CH:27][CH:28]=5)[O:20][N:19]=4)[CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10]2)[CH2:4][O:3]1.[Na+].[I-].CO>CC#N.[Si](Cl)(C)(C)C>[NH2:32][C:5]([CH2:8][N:9]1[C:17]2[C:12](=[C:13]([C:18]3[N:22]=[C:21]([C:23]4[CH:24]=[N:25][C:26]([CH2:29][CH2:30][CH3:31])=[CH:27][CH:28]=4)[O:20][N:19]=3)[CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10]1)([CH2:4][OH:3])[CH2:6][OH:7]

Participants

6

Reactant 3

HCID 887MethanolHCID 5238Sodium IodideHCID 66726785tert-Butyl 2,2-dimethyl-5-((4-(5-(6-propylpyridin-3-yl)-1,2,4-oxadiazol-3-yl)indolin-1-yl)methyl)-1,3-dioxan-5-ylcarbamate

Product 1

HCID 461958852-Amino-2-((4-(5-(6-propylpyridin-3-yl)-1,2,4-oxadiazol-3-yl)indolin-1-yl)methyl)propane-1,3-diolYield 49%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6397ChlorotrimethylsilaneSolvent

Procedure

To a solution of the product of Step E (0.018 g; 0.033 mmol), NaI (0.015 g; 0.0981 mmol) in anhydrous CH3CN (0.6 ml), Me3SiCl (0.08 ml) was added at room temperature with stirring under N2. After stirring for 30 min MeOH (0.5 ml) was added and solvents were removed under reduced pressure. The residue was purified by FCC (SiO2; NH4OH saturated CH2Cl2:MeOH 95:5) to give the title compound (0.0066 g; 49%) as colourless solid. 1H-NMR (CDCl3+CD3OD) 0.93 (tr, 3H, J=(Hz); 1.67-1.81 (m, 2H); 2.81 (tr, 2H, J=9 Hz); 2.99 (broad s, CD3OH); 3.07 (s, 2H); 3.26-3.65 (m, 8H); 6.74 (d, 1H, J=9 Hz); 7.15 (m, 1H); 7.31 (d, 1H, J=9 Hz); 7.42 (d, 1H, J=9 Hz); 8.32 (dd, 1H, J=3, 9 Hz); 9.33 (d, 1H, 3 Hz).

Workup

  1. additionwas added
  2. customsolvents were removed under reduced pressure
  3. customThe residue was purified by FCC (SiO2; NH4OH saturated CH2Cl2:MeOH 95:5)

Sources & evidence

ORD record
ord-64fa259fa00841009b64293144675c67
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Reaction notes

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