5-(Chloromethyl)-1,2,3-trimethoxybenzene → HCID 178491928, compound

HRID 77517

Reaction equation

HRID 77517 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([NH:9][C:10]([NH:12][C:13]([C:15]1[C:20]([NH2:21])=[N:19][C:18]([NH2:22])=[C:17]([Cl:23])[N:16]=1)=[O:14])=[NH:11])[CH2:2]2.[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH:31]=[C:32]([O:36][CH3:37])[C:33]=1[O:34][CH3:35])[CH2:29]Cl>CN(C=O)C>[Cl-:23].[NH2:21][C:20]1[C:15]([C:13]([N:12]=[C:10]([NH2:11])[NH:9][CH:3]2[CH:4]3[CH2:7][CH2:8][N+:1]([CH2:29][C:28]4[CH:31]=[C:32]([O:36][CH3:37])[C:33]([O:34][CH3:35])=[C:26]([O:25][CH3:24])[CH:27]=4)([CH2:6][CH2:5]3)[CH2:2]2)=[O:14])=[N:16][C:17]([Cl:23])=[C:18]([NH2:22])[N:19]=1

Participants

4

Reactant 2

HCID 774485-(Chloromethyl)-1,2,3-trimethoxybenzeneHCID 178512394HCID 178512394, compound2×

Product 1

HCID 178491928HCID 178491928, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(1-Aza-bicyclo[2.2.2]oct-3-yl)-N′-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-guanidine (Intermediate 4, 152 mg, content ca. 66%, 0.30 mmol) and 3,4,5-trimethoxybenzyl chloride (Aldrich, 77 mg, 0.36 mmol) is stirred in DMF (1 mL) at r.t. for ca. 18 h. The crude mixture is purified by preparative HPLC (5 mM ammonium formate in H2O: CH3CN gradient). The product thus obtained is triturated with a mixture of diethyl ether (4 mL) and methanol (1.5 mL), collected by filtration and dried under vacuum at 70° C. Further trituration with water (0.3 mL), filtration and drying under vacuum at 70° C. yields the title compound (35 mg).

Workup

  1. customThe crude mixture is purified by preparative HPLC (5 mM ammonium formate in H2O: CH3CN gradient)
  2. customThe product thus obtained
  3. customis triturated with a mixture of diethyl ether (4 mL) and methanol (1.5 mL)
  4. filtrationcollected by filtration
  5. customdried under vacuum at 70° C
  6. filtrationFurther trituration with water (0.3 mL), filtration
  7. customdrying under vacuum at 70° C.

Sources & evidence

ORD record
ord-580fc6527acf4792bf8acfdf329ed787
Source dataset
uspto-grants-2014_09
Patent number
US08841309B2

Linked notes

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