Triethylamine → Tert-butyl 2-(2-((1-benzylpiperidine-4-yl)(methyl)amino)-2-oxoethoxy)-4,6-dimethylpyrimidine-5-ylcarbamate

HRID 2046324Notes

Reaction equation

HRID 2046324 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[C:10]([CH3:21])=[N:11][C:12]([O:16][CH2:17][C:18]([OH:20])=O)=[N:13][C:14]=1[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:22]([N:29]1[CH2:34][CH2:33][CH:32]([NH:35][CH3:36])[CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>C(#N)C>[CH2:22]([N:29]1[CH2:34][CH2:33][CH:32]([N:35]([CH3:36])[C:18](=[O:20])[CH2:17][O:16][C:12]2[N:13]=[C:14]([CH3:15])[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[C:10]([CH3:21])[N:11]=2)[CH2:31][CH2:30]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 41361281-benzyl-N-methylpiperidin-4-amineHCID 593361682-(5-(Tert-butoxycarbonylamino)-4,6-dimethylpyrimidine-2-yloxy)acetic acid

Product 1

HCID 59336118Tert-butyl 2-(2-((1-benzylpiperidine-4-yl)(methyl)amino)-2-oxoethoxy)-4,6-dimethylpyrimidine-5-ylcarbamateYield 150.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

Compound 9 (74.74 g), 1-benzyl-N-methylpiperidine-4-amine (66.78 g: 1.3 eq.) and triethylamine (127.20 g: 5 eq.) were suspended in acetonitrile (800 mL). While the suspension was cooled on ice, a 50% propanephosphonic acid anhydride ethyl acetate solution (191.99 g) was added portionwise. The equipment used to add 50% propanephosphonic acid anhydride ethyl acetate solution was thoroughly washed with acetonitrile (192 mL) and stirred at room temperature (20 to 30° C.) overnight. Subsequently, the mixture was concentrated under reduced pressure. To the resulting residue, chloroform (250 mL) and a saturated aqueous sodium bicarbonate solution (140 mL) were sequentially added and the mixture was transferred to a separation funnel. The reaction container was thoroughly washed with chloroform (175 mL) and separation was performed. Once the organic layer was separated, chloroform (175 mL) was added to the aqueous layer and separation was performed again. The collected organic layer was dried over magnesium sulfate and was suction-filtered. The filtrate was evaporated under reduced pressure to give 183.27 g of the crude desired product of Compound 30 as a yellow amorphous.

Workup

  1. temperatureWhile the suspension was cooled on ice
  2. washwas thoroughly washed with acetonitrile (192 mL)
  3. concentrationSubsequently, the mixture was concentrated under reduced pressure
  4. additionTo the resulting residue, chloroform (250 mL) and a saturated aqueous sodium bicarbonate solution (140 mL) were sequentially added
  5. customthe mixture was transferred to a separation funnel
  6. washThe reaction container was thoroughly washed with chloroform (175 mL) and separation
  7. customOnce the organic layer was separated
  8. additionchloroform (175 mL) was added to the aqueous layer and separation
  9. dry with materialThe collected organic layer was dried over magnesium sulfate
  10. filtrationwas suction-filtered
  11. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-bca0fc3da05e48f8b6a96ac97e5d6631
Source dataset
uspto-grants-2013_11
Patent number
US08592435B2

Reaction notes

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