Triethylamine → 3-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole-6-carboxylic acid

HRID 1435046Notes

Reaction equation

HRID 1435046 reaction equation
[CH3:1][C:2]1([CH3:36])[CH2:7][CH:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[C:23]4[C:18](=[CH:19][C:20]([CH2:24][OH:25])=[CH:21][CH:22]=4)[N:17]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH2:5][C:4]([CH3:35])([CH3:34])[NH:3]1.CCN(CC)CC.P([O-])(O)(O)=[O:45].[Na+].Cl([O-])=O.[Na+]>CS(C)=O.O.CCOC(C)=O>[CH3:1][C:2]1([CH3:36])[CH2:7][CH:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[C:23]4[C:18](=[CH:19][C:20]([C:24]([OH:45])=[O:25])=[CH:21][CH:22]=4)[N:17]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:32])([CH3:31])[CH3:33])[CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH2:5][C:4]([CH3:35])([CH3:34])[NH:3]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 57936184[3-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-6-yl]-methanol

Product 1

HCID 579361353-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole-6-carboxylic acid

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [3-[2-(2,2,6,6-Tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-6-yl]-methanol (7.20 g, 14.1 mmol) in DMSO (35 ml) and Et3N (31.4 ml, 226 mmol) was added a solution of sulfur trioxide pyridine complex (6.73 g, 42.3 mmol) in DMSO (35 ml). After stirring for 2 h at room temperature, the reaction mixture was poured into EtOAc and the organic phase was washed with water. The organic layer was dried and concentrated. The crude product was dissolved in tert-butanol (645 ml) and 2-methyl-2-butene (100 ml). Then sodium dihydrogenphosphate (4.19 g, 35.0 mmol) dissolved in water (50 ml) was added followed by sodium chlorite (7.91 g, 70.0 mmol) dissolved in water (75 ml) The reaction mixture was stirred overnight and concentrated and diluted with EtOAc upon which a yellow solid was obtained which was used without further purification. Yield: 5.00 g (69%).

Workup

  1. washthe organic phase was washed with water
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. dissolutionThe crude product was dissolved in tert-butanol (645 ml)
  5. additionwas added
  6. stirringwas stirred overnight
  7. concentrationconcentrated
  8. additiondiluted with EtOAc upon which a yellow solid
  9. customwas obtained which
  10. customwas used without further purification

Sources & evidence

ORD record
ord-5d6cd8c208264bd8a7b0b742ac075380
Source dataset
uspto-grants-2009_11
Patent number
US07615562B2

Reaction notes

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