Hydrochloric Acid → HCID 11603737, compound

HRID 421812Notes

Reaction equation

HRID 421812 reaction equation
Cl.CC(Cl)=O.[C:6]([O:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[C:22]([NH:27][C:28]([NH:30][C:31]3[CH:32]=[N:33][C:34]([CH3:37])=[CH:35][CH:36]=3)=[O:29])[CH:21]=2)[CH2:15][CH2:14]1)=[O:12])(C)(C)C>O1CCOCC1>[CH3:6][O:10][C:11]([N:13]1[CH2:14][CH2:15][N:16]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[C:22]([NH:27][C:28]([NH:30][C:31]3[CH:32]=[N:33][C:34]([CH3:37])=[CH:35][CH:36]=3)=[O:29])[CH:21]=2)[CH2:17][CH2:18]1)=[O:12]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 57597087HCID 57597087, compound2×

Product 1

HCID 11603737HCID 11603737, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To 1.0 eq of 4-{4-fluoro-3-[3-(6-methyl-pyridin-3-yl)-ureido]-benzyl}-piperazine-1-carboxylic acid tert-butyl ester (2D) in MeOH (about 0.1 M 2D in MeOH) was added 2 volumes of HCl in dioxane (4 N) and the reaction mixture stirred at 50° C. for 15 min and evaporated to a solid. The solid was combined with DCM and treated with approximately 5 eq of TEA and split into 3 equal portions of reaction mixture A. One portion of the reaction mixture A was treated with 1.2 eq of methyl carbonyl chloride and stirred overnight. The resultant mixture was concentrated and purified by reversed phase HPLC to afford 4-{4-fluoro-3-[3-(6-methyl-pyridin-3-yl)-ureido]-benzyl}-piperazine-1-carboxylic acid methyl ester. MS 402 (M+H). A second portion of the reaction mixture A was treated with 1.2 eq of dimethylsulfamoyl chloride and stirred overnight. The resultant mixture was concentrated and purified by reversed phase HPLC to afford 4-{4-fluoro-3-[3-(6-methyl-pyridin-3-yl)-ureido]-benzyl}-piperazine-1-sulfonic acid dimethylamide. MS 451 (M+H).

Workup

  1. customevaporated to a solid
  2. customsplit into 3 equal portions of reaction mixture A
  3. stirringstirred overnight
  4. concentrationThe resultant mixture was concentrated
  5. custompurified by reversed phase HPLC

Sources & evidence

ORD record
ord-c09507f129914a35978befe222b042ce
Source dataset
uspto-grants-2012_01
Patent number
US08101617B2

Reaction notes

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