Phosphoric Acid → 4-(2-Chloro-pyrido[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 131115Notes

Reaction equation

HRID 131115 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH:11]=[CH:10][CH:9]=[N:8][C:6]=2[N:7]=1.NC1N=CC=CC=1C(O)=O.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].CCN(C(C)C)C(C)C.P(=O)(O)(O)O>C(O)C.CO>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][N:33]([C:4]2[C:5]3[CH:11]=[CH:10][CH:9]=[N:8][C:6]=3[N:7]=[C:2]([Cl:1])[N:3]=2)[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

8

Reactant 5

HCID 1004Phosphoric AcidHCID 729302-Aminonicotinic acidHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 222222282,4-Dichloro-pyrido[2,3-d]pyrimidine

Product 1

HCID 597321274-(2-Chloro-pyrido[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl esterYield 40%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

A mixture of 2,4-dichloro-pyrido[2,3-d]pyrimidine (150 mg, 0.75 mmol, 1 eq) [prepared from 2-aminonicotinic acid by the methods of Robins et al. (J. Am. Chem. Soc. 1955, 77, 1045.) and Oakes et al. (J. Chem. Soc. 1956, 1045.)], N-t-butoxycarbonyl piperazine (147 mg, 0.787 mmol, 1.05 eq) and Hunig's base (0.39 mL, 2.25 mmol, 3 eq) in ethanol (2.5 mL) was stirred at rt for 17 hr. The white solid was collected by filtration, washed with water and cold ethanol, and dried to afford C1.1 (105 mg, 40% yield). LC/MS: 350.41 [M+H]+; HPLC: >95% at 1.44 min (Xterra 5 μm C18 column 4.6×30 mm, 10-90% aqueous methanol over 2 min containing 0.2% phosphoric acid, 5 mL/min, monitoring at 254 nm).

Workup

  1. filtrationThe white solid was collected by filtration
  2. washwashed with water and cold ethanol
  3. customdried
  4. customto afford C1.1 (105 mg, 40% yield)

Sources & evidence

ORD record
ord-467352c9ade34758b898e0f93e8468b3
Source dataset
uspto-grants-2008_06
Patent number
US07384937B2

Reaction notes

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