Isopropyl Acetate → HCID 59451925, 화합물

HRID 1971257

반응식

HRID 1971257 반응식
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

참가 물질

12

반응물 5

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

생성물 1

HCID 59451925HCID 59451925, 화합물

시약·촉매·용매 6

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매

반응 조건

온도
120 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7347959fe1b54d0dbd44bd91dc69f56b
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431593B2

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