Diisopropylethylamine → HCID 86651826, compound

HRID 1916130Notes

Reaction equation

HRID 1916130 reaction equation
[Br:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[NH2:10][C@H:11]1[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1.C(N(C(C)C)CC)(C)C>ClC(Cl)C>[C:20]([O:19][C:17]([N:13]1[CH2:14][CH2:15][CH2:16][C@H:11]([NH:10][C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]([Cl:8])[N:4]=2)[CH2:12]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2899735-Bromo-2,4-dichloropyrimidineHCID 1501975tert-butyl (3S)-3-aminopiperidine-1-carboxylate

Product 1

HCID 86651826HCID 86651826, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution 5-bromo-2,4-dichloro-pyrimidine 4 g, 17.6 mmol), (S)-tert-butyl 3-aminopiperidine-1-carboxylate (3.6 g, 17.6 mmol) and diisopropylethylamine (3.1 ml, 18 mmol) in dichloroethane (200 ml) was warmed to 40-50° C. for 16 hours. The reaction was cooled and washed with water, dried (MgSO4), and filtered. The oil was purified by silica gel chromatography (10-25% ethyl acetate/hexane) to give (S)-3-(5-bromo-2-chloro-pyrimidin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester as an oil that was taken to the next step. The oil was diluted with dichloromethane (100 ml) cooled to 5° C. and treated with trifluoroacetic acid (40 ml). After stirring at room temperature for 5 hours, all solvent was evaporated. The residue was dissolved in chloroform (150 ml) and washed with cold dilute aqueous sodium carbonate. The organics were dried (MgSO4) and evaporated to give an oil that solidified on standing in ether/hexane to give 3.5 g (68%) of (5-bromo-2-chloro-pyrimidin-4-yl)-(S)-piperidin-3-yl-amine as a solid. 1H NMR (300 MHz), dmso-d) δ ppm, 8.23 (s, 1H), 7.17 (s, 1H), 3.99 (m, 1H).

Workup

  1. temperatureThe reaction was cooled
  2. washwashed with water
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customThe oil was purified by silica gel chromatography (10-25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4fb07956e29844f8a90b16fcf7a47f1b
Source dataset
uspto-grants-2013_12
Patent number
US08618103B2

Reaction notes

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