Diisopropylethylamine → 5-bromo-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

HRID 415410Notes

Reaction equation

HRID 415410 reaction equation
Cl.[F:2][C:3]1[CH:4]=[N:5][C:6]([C@@H:9]([NH2:11])[CH3:10])=[N:7][CH:8]=1.[Br:12][C:13]1[C:14]([NH:20][C:21]2[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=2)=[N:15][C:16](Cl)=[N:17][CH:18]=1.CCN(C(C)C)C(C)C>CCCCO>[Br:12][C:13]1[C:14]([NH:20][C:21]2[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=2)=[N:15][C:16]([NH:11][C@H:9]([C:6]2[N:7]=[CH:8][C:3]([F:2])=[CH:4][N:5]=2)[CH3:10])=[N:17][CH:18]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 509936455-bromo-2-chloro-N-(5-methyl-1H-pyrazol-3-yl)-4-PyrimidinamineHCID 66624037(S)-1-(5-Fluoropyrimidin-2-yl)ethanamine hydrochloride

Product 1

HCID 509937245-bromo-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamineYield 47%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
165 °C

Procedure

To a microwave vial was added (S)-1-(5-fluoropyrimidin-2-yl)ethanamine hydrochloride (Method 7, 369 mg, 2.08 mmol), 5-bromo-2-chloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (Method 38, 500 mg, 1.73 mmol), and DIEA (468 mg, 3.8 mmol). Anhydrous n-BuOH (5 mL) was added, and the vial was heated in microwave oven at 165° C. for 5 hours. The reaction mixture was concentrated. The resulting residue was separated by silica gel column to afford desired product (320 mg, 47%). LC-MS, 393 (M+1). 1H NMR δ 12.02 (s, 1H), 8.82 (s, 2H), 7.94 (s, 1H), 7.48 (s, 0.55H), 5.90 (s, 0.41H), 5.09 (s, 1H), 2.19 (m, 3H), 1.49 (m, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customThe resulting residue was separated by silica gel column

Sources & evidence

ORD record
ord-57ceb7ecf7814e14bc2212d72c38940c
Source dataset
uspto-grants-2012_01
Patent number
US08088784B2

Reaction notes

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