Ethyl isocyanate → HCID 67314489, compound

HRID 2179624Notes

Reaction equation

HRID 2179624 reaction equation
C(N(CC)CC)C.[CH2:8]([N:10]=[C:11]=[O:12])[CH3:9].[ClH:13].[N:14]12[CH2:21][CH2:20][CH:17]([CH2:18][CH2:19]1)[C@@H:16]([NH:22][C:23]([C:25]1[S:26][C:27]3[C:33]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[CH2:40][OH:41])=[CH:32][CH:31]=[CH:30][C:28]=3[CH:29]=1)=[O:24])[CH2:15]2.C1COCC1>CN(C=O)C>[ClH:13].[CH2:8]([NH:10][C:11](=[O:12])[O:41][CH2:40][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[C:33]1[C:27]2[S:26][C:25]([C:23]([NH:22][C@@H:16]3[CH:17]4[CH2:18][CH2:19][N:14]([CH2:21][CH2:20]4)[CH2:15]3)=[O:24])=[CH:29][C:28]=2[CH:30]=[CH:31][CH:32]=1)[CH3:9]

Participants

6

Reactant 4

HCID 8022Ethyl isocyanate2×HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 67313750HCID 67313750, compound

Product 1

HCID 67314489HCID 67314489, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

32.5 μl (0.23 mmol) of triethylamine and 16.6 mg (0.23 mmol) of ethyl 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 16.6 mg (0.23 mmol) of ethyl 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 28 mg (47% 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-2c712e2542b44a66a8b19f23fea7e42f
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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