Isopropyl Acetate → HCID 59451925、化合物

HRID 1971257

反応式

HRID 1971257 の反応式
Cl[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[N:5]=[CH:4][CH:3]=1.Cl.[C:12]12(NC)[CH2:21][CH:16]3[CH2:17][CH:18]([CH2:20][CH:14]([CH2:15]3)[CH2:13]1)[CH2:19]2.[Cl-].Cl[C:26]1N(C)CC[N+:27]=1[CH3:32].[OH-].[Na+].C([O:38]C(C)=O)(C)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C(#N)C.O.CN(C=O)C>[C:12]12([CH2:32][NH:27][C:26]([C:2]3[N:7]4[CH:8]=[CH:9][N:10]=[C:6]4[N:5]=[CH:4][CH:3]=3)=[O:38])[CH2:13][CH:14]3[CH2:15][CH:16]([CH2:17][CH:18]([CH2:20]3)[CH2:19]1)[CH2:21]2

参加物

12

反応物 5

HCID 7915Isopropyl AcetateHCID 14798Sodium HydroxideHCID 19477N-methyladamantan-1-amine hydrochlorideHCID 101763062-Chloro-1,3-dimethylimidazolinium chlorideHCID 469120805-Chloroimidazo[1,2-a]pyrimidine

生成物 1

HCID 59451925HCID 59451925、化合物

試薬・触媒・溶媒 6

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
120 °C

実験手順

In a ½ dram vial, 5-chloro-imidazo[1,2-a]pyrimidine (20.2 mg, 0.13 mmol), Zn(CN)2 (9.3 mg, 0.079 mmol), Pd2(dba)3 (3.0 mg, 0.003 mmol) and DPPF (3.6 mg, 0.006 mmol) are treated with DMF (300 μL) and H2O (3 μl). The vial is flushed and then sealed under argon and heated to 120° C. overnight. At RT, the vial is treated with NaOH (1M, 0.5 mL) and i-PrOAc (0.5 mL), and the upper organic layer is purified via strong cation exchange chromatography. The base-eluted solution is concentrated to dryness and treated with HCl (conc., 0.1 mL) and shaken at RT for 1 h and then at 100° C. for an additional 1 h. The reaction is concentrated to dryness under a stream of nitrogen and treated with adamantan-1-yl-methylamine hydrochloride (8.1 mg, 0.040 mmol), TEA (10% (v/v) ACN, 200 μL), and 2-chloro-1,3-dimethyl-4,5-dihydro-3H-imidazolium chloride (0.2 M ACN, 200 μL, 0.040 mmol). The reaction is sealed under nitrogen and shaken at RT for 1 h. NaOH (1M, 0.5 mL) and i-PrOAc (0.5 mL) are added, and the upper organic layer is removed and concentrated to dryness. The residue is purified via silica gel chromatography using EtOAc followed by TEA/MeOH/EtOAc (2.5:2.5:95% v/v/v) to afford the title compound. NMR (400 MHz, CDCl3) δ 1.59 (m, 6H), 1.64 (m, 3H), 1.72 (m, 3H), 1.99 (m, 3H), 3.18 (d, J=6.4, 2H), 7.68 (d, J=1.2, 1H), 7.83 (d, J=6.8, 1H), 7.99 (d, J=1.6, 1H), 8.12 (bs, 1H), 8.58 (d, J=6.8, 1H).

後処理

  1. customThe vial is flushed
  2. customsealed under argon
  3. additionAt RT, the vial is treated with NaOH (1M, 0.5 mL) and i-PrOAc (0.5 mL)
  4. customthe upper organic layer is purified via strong cation exchange chromatography
  5. concentrationThe base-eluted solution is concentrated to dryness
  6. additiontreated with HCl (conc., 0.1 mL)
  7. waitat 100° C. for an additional 1 h
  8. concentrationThe reaction is concentrated to dryness under a stream of nitrogen
  9. customThe reaction is sealed under nitrogen
  10. stirringshaken at RT for 1 h
  11. customthe upper organic layer is removed
  12. concentrationconcentrated to dryness
  13. customThe residue is purified via silica gel chromatography

出典と根拠

ORDレコード
ord-7347959fe1b54d0dbd44bd91dc69f56b
出典データセット
uspto-grants-2013_04
特許番号
US08431593B2

関連ノート

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