tert-Butyl piperazine-1-carboxylate → 4-[7-(4-Methoxy-benzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1192426Notes

Reaction equation

HRID 1192426 reaction equation
Cl[C:2]1[C:3]2[CH2:10][CH2:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:20]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C(O[K])(C)(C)C>CN1C(=O)CCC1.C(OCC)(=O)C>[C:23]([O:22][C:20]([N:27]1[CH2:32][CH2:31][N:30]([C:2]2[C:3]3[CH2:10][CH2:9][N:8]([CH2:11][C:12]4[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=4)[C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:29][CH2:28]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 529881474-chloro-7-(4-methoxybenzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidineHCID 178418922HCID 178418922, compound

Product 1

HCID 675396394-[7-(4-Methoxy-benzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl esterYield 57.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 4-Chloro-7-(4-methoxy-benzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine (0.36 g, 1.31 mmol), 1-Boc-piperazine (1.0 g, 5.37 mmol) and tBuOK (0.18 g, 1.60 mmol) in NMP (20 mL) was heated to 128° C. for 20 hours. After cooling, the mixture was diluted with 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-[7-(4-Methoxy-benzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.32 g, 57%). 1H NMR (CDCl3, 400 MHz) δ 8.17 (s, 1H), 7.20 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 4.50 (s, 2H), 3.79 (s, 3H), 3.59 (m, 4H), 3.48 (m, 4H), 3.35 (m, 2H), 3.30 (m, 2H), 1.49 (s, 9H). MS (APCI+) [M+H]+426.

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-eea971eee96a4bac87d82340462993b6
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

Loading…