Methanol → HCID 89422597, compound

HRID 1752442Notes

Reaction equation

HRID 1752442 reaction equation
[C:1]([CH:4]1[N:9]([C:10]2[CH:15]=[C:14]([C:16](=[O:18])[NH2:17])[N:13]=[C:12]([Cl:19])[N:11]=2)[CH2:8][CH2:7][N:6](C(OC(C)(C)C)=O)[CH2:5]1)(=[O:3])[NH2:2].CO>O1CCOCC1.Cl>[ClH:19].[C:1]([CH:4]1[CH2:5][NH:6][CH2:7][CH2:8][N:9]1[C:10]1[N:11]=[C:12]([Cl:19])[N:13]=[C:14]([C:16]([NH2:17])=[O:18])[CH:15]=1)(=[O:3])[NH2:2]

Participants

5

Reactant 2

HCID 887Methanol2×HCID 89422675HCID 89422675, compound

Product 1

HCID 89422597HCID 89422597, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 312751,4-DioxaneSolvent4×

Procedure

To a solution of tert-butyl 3-carbamoyl-4-(6-carbamoyl-2-chloropyrimidin-4-yl)piperazine-1-carboxylate (4.744 g, 12.33 mmol) in dioxane (25 mL) was added 4M HCl in dioxane (5.0 mL, 20.0 mmol). After stirring overnight the reaction was diluted with additional dioxane (25 mL) and 4M HCl in dioxane (5.0 mL, 20.0 mmol). After 5 h, MeOH (10 mL) was added. After stirring overnight more MeOH (10 mL) was added. After stirring one more night the reaction was evaporated in vacuo to give crude 6-(2-carbamoylpiperazin-1-yl)-2-chloropyrimidine-4-carboxamide hydrochloride. The crude hydrochloride salt was suspended in THF (50 mL). To this was added iPr2NEt (7.10 mL, 40.8 mmol) and methyl iodide (0.85 mL, 13.7 mmol). The reaction vessel was sealed and heated at 70° C. for 5 h. The reaction mixture was cooled and partitioned between EtOAc (100 mL) and water (50 mL). The organics were isolated and saved. 1N aqueous NaOH was added to the aqueous layer then it was extracted with EtOAc (100 mL). These organics were also isolated and saved. Once more, 1N aqueous NaOH was added to the aqueous layer then it was extracted with EtOAc (100 mL). The organics were isolated and combined with the other batches of organic extracts. The combined organics were dried over Na2SO4, filtered, and evaporated in vacuo. The solid residue was triturated with MeOH (5 mL), filtered, and washed with MeOH (1×2 mL). The solid was dried under vacuum at 40° C. to give 6-(2-carbamoyl-4-methylpiperazin-1-yl)-2-chloropyrimidine-4-carboxamide as a cream-colored powder (0.924 g, 3.09 mmol, 25% yield). LC/MS: m/z=299.1 [M+H]+.

Workup

  1. waitAfter 5 h
  2. additionwas added
  3. stirringAfter stirring one more night the reaction
  4. customwas evaporated in vacuo

Sources & evidence

ORD record
ord-0eccfb7f6bdb44ff9e548c1c1850be1a
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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