Chlorosulfonyl isocyanate → 2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5H-pyrrolo[2,3-b]pyrazine-7-carbonitrile

HRID 1052266Notes

Reaction equation

HRID 1052266 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][C:13]2[N:14]=[C:15]3[CH:21]=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([N:28]5[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]5)=[CH:24][CH:23]=4)[NH:19][C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.ClS([N:39]=[C:40]=O)(=O)=O>CN(C)C=O>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([CH2:11][CH2:12][C:13]2[N:14]=[C:15]3[C:21]([C:40]#[N:39])=[C:20]([C:22]4[CH:23]=[CH:24][C:25]([N:28]5[CH2:29][CH2:30][N:31]([CH3:34])[CH2:32][CH2:33]5)=[CH:26][CH:27]=4)[NH:19][C:16]3=[N:17][CH:18]=2)[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1

Participants

4

Reactant 2

HCID 70918Chlorosulfonyl isocyanateHCID 727924822-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 730568412-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5H-pyrrolo[2,3-b]pyrazine-7-carbonitrileYield 22.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[4-(4-methylpiperazin-1-yl)phenyl]-5H-pyrrolo[2,3-b]pyrazine (from Example 1, Step 5, 50.0 mg, 10.9 μmol) in N,N-dimethylformamide (2 mL), chlorosulfonyl isocyanate (24.0 μL, 27.6 μmol) was added at 0° C. The reaction mixture was then warmed to ambient temperature and kept stirring overnight. The volatiles were removed and the residue was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (1.2 mg) as its TFA salt. LCMS calculated for C28H31N6O2 (M+H)+: m/z=483.2. Found: 483.2.

Workup

  1. customThe volatiles were removed
  2. customthe residue was purified on RP-HPLC (XBridge C18 column
  3. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-5cda071c4d9e438e9e4af47556509fda
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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