Bpr-0L075 → tert-Butyl 5-((6-methoxy-3-(3,4,5-trimethoxybenzoyl)-1H-indol-1-yl)methyl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamate

HRID 710367Notes

Reaction equation

HRID 710367 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:12]([C:14]3[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=3)=[O:13])=[CH:8][NH:9]2)=[CH:5][CH:4]=1.CS(O[CH2:31][C:32]1([NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][O:36][C:35]([CH3:39])([CH3:38])[O:34][CH2:33]1)(=O)=O>CN(C=O)C.CCOCC>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:12](=[O:13])[C:14]3[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=3)=[CH:8][N:9]2[CH2:31][C:32]2([NH:40][C:41](=[O:42])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:37][O:36][C:35]([CH3:38])([CH3:39])[O:34][CH2:33]2)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 10359957Bpr-0L075HCID 86661783(5-(tert-Butoxycarbonylamino)-2,2-dimethyl-1,3-dioxan-5-yl)methyl methanesulfonate

Product 1

HCID 86661782tert-Butyl 5-((6-methoxy-3-(3,4,5-trimethoxybenzoyl)-1H-indol-1-yl)methyl)-2,2-dimethyl-1,3-dioxan-5-ylcarbamateYield 37.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of the product of Example 13, Step B (0.11 g; 0.32 mmol) in anhydrous DMF (0.6 ml) 60% NaH in mineral oil (0.02 g; 0.5 mmol) was added and the mixture was stirred for 1 h at room temperature under N2. To it, a product of Step A (0.13 g; 0.383 mmol) was added and the resulting mixture was stirred for 3 days at ˜55° C. under N2, cooled to room temperature and diluted to 15 ml with Et2O, washed with H2O, brine, dried over anhydrous MgSO4 and filtered. The filtrate was evaporated to dryness under reduced pressure and the residue was purified by FCC (SiO2, CH2Cl2/EtOAc 8:2) to give the title compound (0.07 g; 37%) as a colourless solid. 1H-NMR (CDCl3) 1.23 (s, 9H); 1.46 (s, 3H); 1.53 (s, 3H); 3.71 (d, 2H, J=11.8 Hz); 3.84-3.94 (m, 15H); 4.12 (s, 1H); 4.76 (s, 2H); 6.96 (dd, 1H, J=2.2, 8.8 Hz); 7.06 (s, 2H); 7.16 (d, 1H, J=2.2 Hz); 7.44 (s, 1H); 8.24 (d, 1H, J=8.8 Hz).

Workup

  1. stirringthe resulting mixture was stirred for 3 days at ˜55° C. under N2
  2. temperaturecooled to room temperature
  3. washwashed with H2O, brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness under reduced pressure
  7. customthe residue was purified by FCC (SiO2, CH2Cl2/EtOAc 8:2)

Sources & evidence

ORD record
ord-f3392a9969d341c2b07781da12961bfc
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Reaction notes

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