Diisopropylethylamine → [(S)-1-Methyl-2-(7-{[(pyridine-3-carbonyl)-amino]-methyl}-furo[2,3-g]indazol-1-yl)-ethyl]-carbamic acid benzyl ester

HRID 1453901Notes

Reaction equation

HRID 1453901 reaction equation
[CH2:1]([O:8][C:9](=[O:28])[NH:10][C@@H:11]([CH3:27])[CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]3[O:24][C:23]([CH2:25][NH2:26])=[CH:22][C:20]3=2)[CH:15]=[N:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:38](Cl)(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[N:41][CH:40]=1>C1COCC1>[CH2:1]([O:8][C:9](=[O:28])[NH:10][C@@H:11]([CH3:27])[CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]3[O:24][C:23]([CH2:25][NH:26][C:38]([C:39]4[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=4)=[O:45])=[CH:22][C:20]3=2)[CH:15]=[N:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 82604Nicotinoyl chlorideHCID 68858114[(S)-2-(7-Aminomethyl-furo[2,3-g]indazol-1-yl)-1-methylethyl]-carbamic acid benzyl ester

Product 1

HCID 68857650[(S)-1-Methyl-2-(7-{[(pyridine-3-carbonyl)-amino]-methyl}-furo[2,3-g]indazol-1-yl)-ethyl]-carbamic acid benzyl esterYield 39.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the product from Step B (0.32 g, 0.847 mmol) in THF (20 mL) was added polymer supported di-isopropyl ethyl amine (3.86 mmol/g, 0.44 g, 1.69 mmol, 2 eq); this suspension was cooled (ice bath) and nicotinoyl chloride (0.15 g, 0.847 mmol) was added. The ice bath was removed and mixture was stirred for one hour, additional nicotinoyl chloride (50 mg) was added and the mixture was stirred at room temperature overnight. Triethylamine was added and after stirring for 10 min saturated aqueous sodium bicarbonate (150 mL) was added. This mixture was extracted with ethyl acetate (2×100 mL). The combined extracts were dried (MgSO4) and evaporated to an oil which was purified by chromatography (silica gel, hexane/ethyl acetate gradient) to give a solid (0.16 g, 39%): LC/MS m/z 484 [M+H]+.

Workup

  1. additionwas added
  2. customThe ice bath was removed
  3. additionadditional nicotinoyl chloride (50 mg) was added
  4. stirringthe mixture was stirred at room temperature overnight
  5. additionTriethylamine was added
  6. stirringafter stirring for 10 min saturated aqueous sodium bicarbonate (150 mL)
  7. additionwas added
  8. extractionThis mixture was extracted with ethyl acetate (2×100 mL)
  9. dry with materialThe combined extracts were dried (MgSO4)
  10. customevaporated to an oil which
  11. customwas purified by chromatography (silica gel, hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-7eea3a321a924b429d94713b697d73d2
Source dataset
uspto-grants-2009_01
Patent number
US07476687B2

Reaction notes

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