3-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine → 5-(5-bromo-2-(piperazin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine

HRID 538436

反応式

HRID 538436 の反応式
[CH3:1][O:2][C:3]1[C:4]([NH2:18])=[N:5][CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1.Br[C:20]1[N:21]=[C:22]([N:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)[N:23]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:24]=1[Br:25]>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:25][C:24]1[N:23]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:22]([N:34]2[CH2:35][CH2:36][NH:37][CH2:38][CH2:39]2)=[N:21][C:20]=1[C:7]1[CH:8]=[C:3]([O:2][CH3:1])[C:4]([NH2:18])=[N:5][CH:6]=1

参加物

6

反応物 2

HCID 533980593-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 586258311-(4,5-Dibromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)piperazine

生成物 1

HCID 665911525-(5-bromo-2-(piperazin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒HCID 10340Sodium Carbonate溶媒

反応条件

温度
115 °C

実験手順

A mixture of 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (56.2 mg, 0.225 mmol) and 1-(4,5-dibromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)piperazine (90 mg, 0.204 mmol) in DME (2.1 ml) and 2M aqueous Na2CO3 (0.7 ml) was sparged with Ar for 2 min. Pd(Ph3P)4 (23.6 mg, 0.02 mmol) was added. The mixture was sparged with Argon for an additional 2 min and was heated in a sealed tube in a microwave reactor at 115° C. for 15 min. The reaction mixture was extracted with EtOAc (3×15 mL). The combined organic layers were washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude materials of both reactions were combined and purified by preparative TLC (SiO2, 1.0 mm, 90:10 DCM-MeOH) to furnish 5-(5-bromo-2-(piperazin-1-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-3-methoxypyridin-2-amine was isolated as a white solid which was directly used in the next step: LCMS (m/z): 485.2 (MH+), tR=0.56 min.

後処理

  1. customwas sparged with Ar for 2 min
  2. customThe mixture was sparged with Argon for an additional 2 min
  3. extractionThe reaction mixture was extracted with EtOAc (3×15 mL)
  4. washThe combined organic layers were washed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified by preparative TLC (SiO2, 1.0 mm, 90:10 DCM-MeOH)

出典と根拠

ORDレコード
ord-d90e9e33970a457e9fb565f4779a5d49
出典データセット
uspto-grants-2014_10
特許番号
US08865732B2

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