Sodium hydride → HCID 59238656, compound

HRID 552263Notes

Reaction equation

HRID 552263 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([C:10]3[CH2:15][CH2:14][CH:13]([N:16]4[CH2:22][CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[CH2:12][CH:11]=3)[CH:9]=[C:4]2[CH:3]=[CH:2]1.[H-].[Na+].[C:25]([Si:29]([CH3:32])([CH3:31])Cl)([CH3:28])([CH3:27])[CH3:26]>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Si:29]([N:1]1[C:5]2=[N:6][CH:7]=[C:8]([C:10]3[CH2:15][CH2:14][CH:13]([N:16]4[CH2:22][CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[CH2:12][CH:11]=3)[CH:9]=[C:4]2[CH:3]=[CH:2]1)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:32])[CH3:31]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 28928tert-Butyldimethylsilyl chlorideHCID 59238630HCID 59238630, compound

Product 1

HCID 59238656HCID 59238656, compoundYield 87.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a stirred solution of azaindole (XXVa-101) (12.65 g, 42.5 mmol) in DMF (120 mL) was added 60% NaH dispersion in mineral oil (2.04 g, 51.0 mmol) portionwise over 3 min. After 15 min, tert-butyldimethylchlorosilane (8.33 g, 55.3 mmol) was added and the mixture stirred for a further 66 h. The mixture was diluted with EtOAc (150 mL) and saturated NaHCO3 solution (100 mL) and partitioned. The aqueous layer was extracted with EtOAc (4×150 mL) and CH2Cl2 (100 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated to yield a honey coloured viscous oil. This was purified by means of SGC using hexane:CH2Cl2 (gradient elution from 100:0 to 0:100, v/v) followed by CH2Cl2:MeOH (gradient elution from 100:0 to 90:10, v/v) to afford the silylated azaindole (XXVIIa-101) (15.37 g, 87%). 1H NMR (400 MHz, CDCl3) δ 0.62 (s, 6H), 0.92 (s, 9H), 1.68 (m, 1H), 1.87-1.93 (m, 2H), 2.05-2.10 (m, 1H), 2.18-2.26 (m, 1H), 2.36-2.43 (m, 1H), 2.57-2.63 (m, 2H), 2.83-2.86 (m, 5H), 3.75 (t, J=4.7 Hz, 2H), 3.82 (t, J=6.0 Hz, 2H), 6.02-6.05 (m, 1H), 6.49 (d, J=3.5 Hz, 1H), 7.21 (d, J=3.5 Hz, 1H), 7.81 (d, J=2.3 Hz, 1H), 8.33 (d, J=2.3 Hz, 1H).

Workup

  1. custompartitioned
  2. extractionThe aqueous layer was extracted with EtOAc (4×150 mL) and CH2Cl2 (100 mL)
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield a honey
  7. customThis was purified by means of SGC
  8. washMeOH (gradient elution from 100:0 to 90:10

Sources & evidence

ORD record
ord-eec3155f761c4506b9fe17d428319ee1
Source dataset
uspto-grants-2011_05
Patent number
US07951802B2

Reaction notes

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