Tetrahydrofuran → (S)-4-(benzyloxycarbonylamino)-N-{1-[2-(trimethylsilyl)ethoxymethyl]pyrrolo[2,3-b]pyridin-4-yl}thiochromane-7-carboxamide

HRID 585743Notes

Reaction equation

HRID 585743 reaction equation
O1CCCC1.[NH2:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:14]=[CH:15][C:8]=12.C([Li])CCC.[CH2:29]([O:36][C:37]([NH:39][C@@H:40]1[C:49]2[C:44](=[CH:45][C:46]([C:50](Cl)=[O:51])=[CH:47][CH:48]=2)[S:43][CH2:42][CH2:41]1)=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O>[CH2:29]([O:36][C:37]([NH:39][C@@H:40]1[C:49]2[C:44](=[CH:45][C:46]([C:50]([NH:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]4[N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:14]=[CH:15][C:8]=34)=[O:51])=[CH:47][CH:48]=2)[S:43][CH2:42][CH2:41]1)=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 223374571-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-4-amineHCID 87917945(S)-4-(benzyloxycarbonylamino)thiochromane-7-carboxylic acid chlorideHCID 178418339Butyllithium

Product 1

HCID 69619656(S)-4-(benzyloxycarbonylamino)-N-{1-[2-(trimethylsilyl)ethoxymethyl]pyrrolo[2,3-b]pyridin-4-yl}thiochromane-7-carboxamideYield 42.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a tetrahydrofuran solution of 4-amino-1-[2-(trimethylsilyl)ethoxymethyl]pyrrolo[2,3-b]pyridine (1.32 g) was added dropwise n-butyllithium (1.59 M, 3.17 ml) and the mixture was stirred at the same temperature for 15 min. To this solution was added dropwise a tetrahydrofuran solution (20 ml) of (S)-4-(benzyloxycarbonylamino)thiochromane-7-carboxylic acid chloride (4.20 mmol) obtained by a similar reaction step as in Starting Material Synthetic Example 9 at 0° C. The reaction mixture was stirred at room temperature for 5 hr. Water (100 ml) was added and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and purified by silica gel column chromatography (hexane-ethyl acetate) to give the objective (S)-4-(benzyloxycarbonylamino)-N-{1-[2-(trimethylsilyl)ethoxymethyl]pyrrolo[2,3-b]pyridin-4-yl}thiochromane-7-carboxamide (1.06 g) as a pale-brown amorphous solid.

Workup

  1. customobtained by a similar reaction step as
  2. customat 0° C
  3. stirringThe reaction mixture was stirred at room temperature for 5 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe obtained organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated
  8. custompurified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-0847ac71695e469e9dbefe1780be4070
Source dataset
uspto-grants-2005_08
Patent number
US06933305B2

Reaction notes

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