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

HRID 2046342

Reaction equation

HRID 2046342 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].[CH:22]1([CH2:25][N:26]2[CH2:31][CH2:30][CH:29]([NH:32][CH3:33])[CH2:28][CH2:27]2)[CH2:24][CH2:23]1.C(N(CC)CC)C>C(#N)C>[CH:22]1([CH2:25][N:26]2[CH2:31][CH2:30][CH:29]([N:32]([CH3:33])[C:18](=[O:20])[CH2:17][O:16][C:12]3[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]=3)[CH2:28][CH2:27]2)[CH2:23][CH2:24]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 433149081-(cyclopropylmethyl)-N-methylpiperidine-4-amineHCID 593361682-(5-(Tert-butoxycarbonylamino)-4,6-dimethylpyrimidine-2-yloxy)acetic acid

Product 1

HCID 59336181Tert-butyl 2-(2-((1-(cyclopropylmethyl)-piperidine-4-yl)(methyl)amino)-2-oxoethoxy)-4,6-dimethylpyrimidine-5-ylcarbamateYield 52.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

Compound 9 (100 mg), 1-(cyclopropylmethyl)-N-methylpiperidine-4-amine (56.6 mg) and triethylamine (234 μL) were suspended in acetonitrile (2 mL). While the suspension was cooled with ice, a 50% propane phosphonic acid anhydride ethyl acetate solution (273 mg) was added portionwise. The equipment used to add the 50% propane phosphonic acid anhydride ethyl acetate solution was thoroughly washed with acetonitrile (0.5 mL) and was stirred at room temperature (20 to 30° C.) overnight. Subsequently, the reaction mixture was concentrated under reduced pressure and the resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (methylene chloride:methanol=30:1) to give 79 mg (52% yield) of the desired product as a pale yellow amorphous.

Workup

  1. temperatureWhile the suspension was cooled with ice
  2. washwas thoroughly washed with acetonitrile (0.5 mL)
  3. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
  4. customthe resulting residue was purified by amino-coated silica gel (Fuji Sylysia Chemical Ltd.; NH-DM1020) column chromatography (methylene chloride:methanol=30:1)

Sources & evidence

ORD record
ord-b67e05f06fec4231ac930e33e00f1d99
Source dataset
uspto-grants-2013_11
Patent number
US08592435B2

Linked notes

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