Methanol → HCID 69607376, compound

HRID 1244112Notes

Reaction equation

HRID 1244112 reaction equation
C(O[C:4]([C:6]1[C:10]([I:11])=[C:9]([CH3:12])[S:8][C:7]=1[NH:13][C:14](=[O:18])[CH2:15][C:16]#[N:17])=[O:5])C.[H-].[Na+].CO>C1COCC1>[OH:5][C:4]1[C:6]2[C:10]([I:11])=[C:9]([CH3:12])[S:8][C:7]=2[NH:13][C:14](=[O:18])[C:15]=1[C:16]#[N:17]

Participants

5

Reactant 3

HCID 887MethanolHCID 24758Sodium hydrideHCID 69607333HCID 69607333, compound

Product 1

HCID 69607376HCID 69607376, compoundYield 22.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(2-Cyano-acetylamino)-4-iodo-5-methyl-thiophene-3-carboxylic acid ethyl ester (189 mg, 0.5 mmol) was cyclized by NaH in THF at room temperature for 12 h as described in Example 29D. After reaction was finished, methanol (2 mL) was added and the mixture was evaporated. The residue was purified on HPLC to give 4-hydroxy-3-iodo-2methyl-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine-5-cabonitrile (38 mg, 22.9%). This compound (33 mg, 0.1 mmol) was taken up in a Smith Process Vial (2–5 mL), CuI (7.6 mg, 0.04 mmol), Pd(PPh3)2Cl2 (14 mg, 0.02 mmol), DMF (2 ml), diisopro pylamine (1 mL) and phenylacetylene (20.4 mg, 0.2 mmol) were then added sequentially. After degassed, the vial was sealed and stirred at 70° C. for 2 h. The resulting mixture was filtered and the solid was washed with methanol (5 mL×2). The combined organic layers were concentrated under vacuum and purification on HPLC to give title compound (20 mg, 65%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 11.0 (s, 1H), 7.52–7.38 (m, 5H), 2.44 (s, 3H, MS (ESI) m/e 307 (M+H)+, 305 (M−H)−.

Workup

  1. customAfter reaction
  2. customthe mixture was evaporated
  3. customThe residue was purified on HPLC

Sources & evidence

ORD record
ord-d16201f383c94847acde52aab2b71f3d
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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