2,4-dichloro-5H,6H,7H-cyclopenta(d)pyrimidine → 1,1-Dimethylethyl 4-[(2-chloro-6,7-dihydro-5H-cyclopentapyrimidin-4-yl)amino]-1-piperidinecarboxylate

HRID 2242980Notes

Reaction equation

HRID 2242980 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]2[CH2:9][CH2:10][CH2:11][C:4]=2[N:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]>CN(C=O)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:25][C:6]2[C:5]3[CH2:9][CH2:10][CH2:11][C:4]=3[N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

4

Reactant 2

HCID 2313312,4-dichloro-5H,6H,7H-cyclopenta(d)pyrimidineHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 863463121,1-Dimethylethyl 4-[(2-chloro-6,7-dihydro-5H-cyclopentapyrimidin-4-yl)amino]-1-piperidinecarboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2,4-dichloro-6,7-dihydro-5H-cyclopentapyrimidine (2.71 g, 14.34 mmol, 1.0 equiv) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (3.45 g, 17.20 mmol, 1.2 equiv) in anhydrous DMF (40 mL) was heated to 60° C. for 18 h. The organic phase was concentrated under reduced pressure and the crude reaction mixture extracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×50 mL). The combined organic phases were dried over MgSO4 and the product purified with column chromatography on silica eluting with a gradient of heptane/ethyl acetate (14:3→1:1) providing 2.34 g (47%) of the title compound. 1H NMR (300 MHz, DMSO): δ 1.32-1.43 (m, 2H), 1.39 (s, 9H), 1.79-1.82 (m, 2H), 2.0 (quint, J=7.5 Hz, 2H), 2.61 (t, J=7.5 Hz, 2H), 2.70 (t, J=7.5 Hz, 2H), 2.80-2.88 (m, 2H), 3.93-3.98 (m, 2H), 4.04-4.13 (m, 1H), 7.07 (d, J=8.0 Hz, 1H). 13C NMR (75 MHz, DMSO): δ 21.12, 26.42, 28.04, 31.17, 33.19, 42.55, 47.12, 78.53, 114.87, 153.84, 157.95, 159.02, 172.18. MS (ISP): 353.1 [M+H]+.

Workup

  1. concentrationThe organic phase was concentrated under reduced pressure
  2. customthe crude reaction mixture
  3. extractionextracted from a solution of 1 M NaOH (100 mL) with ethyl acetate (3×50 mL)
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. customthe product purified with column chromatography on silica eluting with a gradient of heptane/ethyl acetate (14:3→1:1)

Sources & evidence

ORD record
ord-336acd2bb90e4913b5ab5d1585b42a15
Source dataset
uspto-grants-2010_03
Patent number
US07674804B2

Reaction notes

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