Tetrahydrofuran → HCID 67313605, compound

HRID 1012751Notes

Reaction equation

HRID 1012751 reaction equation
C(N(CC)CC)C.[CH3:8][N:9]=[C:10]=[O:11].[ClH:12].[N:13]12[CH2:20][CH2:19][CH:16]([CH2:17][CH2:18]1)[C@@H:15]([NH:21][C:22]([C:24]1[S:25][C:26]3[C:32]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[CH2:39][OH:40])=[CH:31][CH:30]=[CH:29][C:27]=3[CH:28]=1)=[O:23])[CH2:14]2.C1COCC1>CN(C=O)C>[ClH:12].[CH3:8][NH:9][C:10](=[O:11])[O:40][CH2:39][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[C:32]1[C:26]2[S:25][C:24]([C:22]([NH:21][C@@H:15]3[CH:16]4[CH2:17][CH2:18][N:13]([CH2:20][CH2:19]4)[CH2:14]3)=[O:23])=[CH:28][C:27]=2[CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 12228Methyl Isocyanate2×HCID 67313750HCID 67313750, compound

Product 1

HCID 67313605HCID 67313605, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

32.5 μl (0.23 mmol) of triethylamine and 13.3 mg (0.23 mmol) of methyl isocyanate are added to a suspension of 50 mg (0.12 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-[2-(hydroxymethyl)phenyl]-1-benzothiophene-2-carboxamide hydrochloride (Example 131) in 1 ml of a 5:1 mixture of THF and DMF. After 18 h at room temperature, a further 13.3 mg (0.23 mmol) of methyl isocyanate and a catalytic amount of 4-N,N-dimethylaminopyridine are added. The mixture is stirred at room temperature for a further 18 h. The reaction mixture is concentrated in vacuo and purified by preparative HPLC. The product fractions are concentrated and, after addition of a 5:1 mixture of methanol and 1N hydrochloric acid, again concentrated. Drying under high vacuum results in 18 mg (30% of theory) of the title compound.

Workup

  1. concentrationThe reaction mixture is concentrated in vacuo
  2. custompurified by preparative HPLC
  3. concentrationThe product fractions are concentrated
  4. additionafter addition of a 5:1 mixture of methanol and 1N hydrochloric acid
  5. concentrationagain concentrated
  6. customDrying under high vacuum

Sources & evidence

ORD record
ord-f86229a792d040f78d820bf1ff7cccad
Source dataset
uspto-grants-2011_07
Patent number
US07977485B2

Reaction notes

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