Ethyl Acetate → 4-(5-Methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1192431Notes

Reaction equation

HRID 1192431 reaction equation
Cl[C:2]1[C:3]2[CH:10]([CH3:11])[CH2:9][N:8](CC3C=CC(OC)=CC=3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:21]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].C(O[K])(C)(C)C.C(OCC)(=O)C>CN1C(=O)CCC1>[C:24]([O:23][C:21]([N:28]1[CH2:33][CH2:32][N:31]([C:2]2[C:3]3[CH:10]([CH3:11])[CH2:9][NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:30][CH2:29]1)=[O:22])([CH3:27])([CH3:25])[CH3:26]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 865987414-Chloro-7-(4-methoxy-benzyl)-5-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidineHCID 178418922HCID 178418922, compound

Product 1

HCID 675396654-(5-Methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl esterYield 50%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
128 °C

Procedure

To a solution of 4-Chloro-7-(4-methoxy-benzyl)-5-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine (0.55 g, 1.88 mmol) in NMP (20 mL) were added 1-Boc-piperazine (1.0 g, 5.40 mmol) and tBuOK (0.21 g, 1.88 mmol). The mixture was heated to 128° C. for 30 hours. After cooling, the mixture was diluted by ethyl acetate (500 mL) and washed with water (5×150 mL). The organic phase was dried and concentrated. The residue was subject to column chromatography, eluted by hexane/ethyl acetate (1:1) to give 4-(5-Methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (0.30 g, 36%). 1H NMR (CDCl3, 400 MHz) δ 8.19 (s, 1H), 7.18 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 4.52 (dd, J=27.6 Hz, J=14.8 Hz, 2H), 3.79 (s, 3H), 3.58 (m, 12H), 3.34 (m 1H), 2.95 (m, 1H), 1.48 (s, 9H), 1.15 (d, J=6.8 Hz, 3H). MS (APCI+) [M+H]+440.

Workup

  1. temperatureAfter cooling
  2. washwashed with water (5×150 mL)
  3. customThe organic phase was dried
  4. concentrationconcentrated
  5. washeluted by hexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-2e54a65a1b50464da951c4fa2febcaa7
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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