Azetidine → 2-{4-[4-(Azetidin-1-ylacetyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine hydrochloride

HRID 1441312Notes

Reaction equation

HRID 1441312 reaction equation
[Cl:1][CH2:2][C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:32]=[CH:31][C:14]([NH:15][C:16]3[N:21]=[C:20]([C:22]4[N:26]([CH:27]([CH3:29])[CH3:28])[C:25]([CH3:30])=[N:24][CH:23]=4)[CH:19]=[CH:18][N:17]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1)=[O:4].[NH:33]1[CH2:36][CH2:35][CH2:34]1>CCOC(C)=O>[ClH:1].[N:33]1([CH2:2][C:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]3[CH:32]=[CH:31][C:14]([NH:15][C:16]4[N:21]=[C:20]([C:22]5[N:26]([CH:27]([CH3:29])[CH3:28])[C:25]([CH3:30])=[N:24][CH:23]=5)[CH:19]=[CH:18][N:17]=4)=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)=[O:4])[CH2:36][CH2:35][CH2:34]1

Participants

4

Reactant 2

HCID 10422AzetidineHCID 114765422-{4-[4-(Chloroacetyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

Product 1

HCID 686870802-{4-[4-(Azetidin-1-ylacetyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine hydrochloride

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2-{4-[4-(Chloroacetyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine (Example 24; 0.34 g, 0.75 mmol) and azetidine (2 ml) was stirred for 24 hours at ambient temperature. The solution was diluted with EtOAc (20 ml), washed with aqueous saturated sodium bicarbonate solution (10 ml) and aqueous saturated sodium chloride solution (10 ml), then dried and evaporated at reduced pressure. The residue was purified by chromatography on a 40 g silica column, eluted with a 3% MeOH-ammonia/DCM to 5% MeOH-ammonia/DCM gradient, to give the amine, which was converted to the hydrochloride salt by dissolving in EtOAc (3 ml) and treating with a 1.0 molar solution of ethereal-HCl (0.75 ml). The solid was triturated with ether (20 ml) and filtered to give the title compound (24 mg, 7%). NMR: 9.77 (s, 1H), 8.58 (d, 1H), 8.20 (s, 1H), 7.61 (d, 2H), 7.35-7.24 (m, 2H), 7.13 (d, 1H), 5.64-5.55 (m, 1H), 4.65 (brs, 1H), 4.44 (d, 2H), 4.23-4.11 (m, 2H), 4.09-3.96 (m, 2H), 3.81-3.71 (m, 2H), 3.69-3.59 (m, 2H), 3.42-3.31 (m, 2H), 3.30-3.17 (m, 2H), 2.48-2.24 (m, 2H), 2.81 (s, 3H), 1.48 (d, 6H); m/z 475.

Workup

  1. washwashed with aqueous saturated sodium bicarbonate solution (10 ml) and aqueous saturated sodium chloride solution (10 ml)
  2. customdried
  3. customevaporated at reduced pressure
  4. customThe residue was purified by chromatography on a 40 g silica column
  5. washeluted with a 3% MeOH-ammonia/DCM to 5% MeOH-ammonia/DCM gradient

Sources & evidence

ORD record
ord-80d5bf070b374f459603190997795210
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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