Nitrogen → (R)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol

HRID 717519Notes

Reaction equation

HRID 717519 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:32][CH2:31][C@@H:30]([CH2:33][F:34])[CH2:29]3)=[CH:21][CH:20]=1)[C:13]([C:35]1[CH:40]=[CH:39][C:38]([O:41]CC3C=CC=CC=3)=[CH:37][CH:36]=1)=[C:12]2[CH3:49])C1C=CC=CC=1.N#N>C(OCC)(=O)C.C(O)C.C(OCC)(=O)C.[Pd]>[F:34][CH2:33][C@@H:30]1[CH2:31][CH2:32][N:28]([CH2:27][CH2:26][O:25][C:22]2[CH:23]=[CH:24][C:19]([CH2:18][N:14]3[C:15]4[C:11](=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=4)[C:12]([CH3:49])=[C:13]3[C:35]3[CH:36]=[CH:37][C:38]([OH:41])=[CH:39][CH:40]=3)=[CH:20][CH:21]=2)[CH2:29]1

Participants

6

Reactant 2

HCID 947NitrogenHCID 117774168(R)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-3-methyl-1H-indole

Product 1

HCID 89634483(R)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-olYield 90.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolventHCID 21584252Ethanol ethylacetateSolvent

Procedure

A solution of (R)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-3-methyl-1H-indole (263 mg, 0.40 mmol) in ethyl acetate/ethanol (4:1, 6 mL) was degassed with three vacuum/N2 cycles. To this solution was added 10% Pd on carbon (120 mg, 0.11 mmol) and then the needle of a H2 balloon was placed into the reaction flask. The mixture was stirred at room temperature for 15 hrs then diluted with ethyl acetate, filtered through Celite and concentrated. The residue was dried further on high vacuum to give 171 mg of (R)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol as a beige solid. 1H NMR (400 MHz, DMSO-d6): δ 9.67 (s, 1H), 8.69 (s, 1H), 7.16 (d, 2H), 7.06 (d, 1H), 6.85 (d, 2H), 6.80 (d, 1H), 6.75 (s, 4H), 6.57 (dd, 1H), 5.10 (s, 2H), 4.35-4.30 (m, 1H), 4.23-4.18 (m, 1H), 3.94 (t, 2H), 2.70 (t, 2H), 2.62 (t, 1H), 2.56-2.40 (m, 3H), 2.38-2.31 (m, 1H), 2.10 (s, 3H), 1.87-1.76 (m, 1H), 1.40-1.31 (m, 1H). LCMS: 475.2 (M+H)+.

Workup

  1. filtrationfiltered through Celite
  2. concentrationconcentrated
  3. customThe residue was dried further on high vacuum

Sources & evidence

ORD record
ord-f84c21798bba4379b3dd3541cd6dae2a
Source dataset
uspto-grants-2015_11
Patent number
US09193714B2

Reaction notes

Loading…