Diisopropylethylamine → HCID 178480515, compound

HRID 2404466Notes

Reaction equation

HRID 2404466 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]2[NH:6][C:7]([CH:9]([O:20][CH:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[C:10]3[CH:11]=[C:12]([S:16][CH2:17][CH2:18][NH2:19])[CH:13]=[CH:14][CH:15]=3)=[N:8][C:4]=2[CH:3]=1.C(N1C=CC([C:42](=[NH:44])[NH2:43])N1C(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(N(C(C)C)CC)(C)C>C(#N)C>[F:1][C:2]1[CH:29]=[CH:28][C:5]2[NH:6][C:7]([CH:9]([O:20][CH:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[C:10]3[CH:11]=[C:12]([S:16][CH2:17][CH2:18][NH:19][C:42]([NH2:44])=[NH:43])[CH:13]=[CH:14][CH:15]=3)=[N:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86695324N,N'-bis-Boc-guanylpyrazoleHCID 178480513HCID 178480513, compound

Product 1

HCID 178480515HCID 178480515, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-{3-[(5-fluoro-1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenylsulfanyl}ethylamine (example 437B, 230 mg) in acetonitrile (15 mL) is added is added N,N′-bis-Boc-guanylpyrazole (172 mg) and diisopropylethylamine (1 equivalent) at room temperature. The mixture is stirred at room temperature for 3 h. The solvent and volatiles are removed under reduced pressure. The residue is purified by chromatography on silica gel (gradient dichloromethane/methanol from 100/0 to 95/5). The residue is then dissolved in 5N aqueous hydrochloric acid (8 mL) and the solution is stirred overnight at room temperature. The solvent and volatiles are removed under reduced pressure and the residue is triturated with diethyl ether and filtered to afford N-(2-{3-[(5-fluoro-1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenylsulfanyl}ethyl) guanidine trihydrochlorhide as a white crystalline solid melting at 170° C.

Workup

  1. customThe solvent and volatiles are removed under reduced pressure
  2. customThe residue is purified by chromatography on silica gel (gradient dichloromethane/methanol from 100/0 to 95/5)
  3. dissolutionThe residue is then dissolved in 5N aqueous hydrochloric acid (8 mL)
  4. stirringthe solution is stirred overnight at room temperature
  5. customThe solvent and volatiles are removed under reduced pressure
  6. customthe residue is triturated with diethyl ether
  7. filtrationfiltered

Sources & evidence

ORD record
ord-c661de69f91a47df819a5f618e2eddb1
Source dataset
uspto-grants-2014_08
Patent number
US08802664B2

Reaction notes

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