Sodium Carbonate → 4-(4-(6-amino-5-methoxypyridin-3-yl)-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine

HRID 538412노트

반응식

HRID 538412 반응식
Br[C:2]1[N:3]=[C:4]([C:30]([CH3:33])([CH3:32])[CH3:31])[N:5]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]2[CH:19]=[CH:18][N:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[N:8]=1.[CH3:34][O:35][C:36]1[C:37]([NH2:51])=[N:38][CH:39]=[C:40](B2OC(C)(C)C(C)(C)O2)N=1.[C:52]([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[NH2:51][C:37]1[N:38]=[CH:39][C:40]([C:2]2[N:3]=[C:4]([C:30]([CH3:33])([CH3:32])[CH3:31])[N:5]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:6]=2[C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[C:16]([O:20][CH3:21])[CH:15]=3)[N:8]=2)=[CH:52][C:36]=1[O:35][CH3:34]

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 533986313-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amineHCID 665912424-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine

생성물 1

HCID 665913124-(4-(6-amino-5-methoxypyridin-3-yl)-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine수율 93.1%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
100 °C

실험 절차

A mixture of 4-(4-bromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine (100 mg, 0.19 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amine (118 mg, 0.47 mmol, Example 18, Step 2), aqueous 2.0 M Na2CO3 solution (1 ml, 2.0 mmol), and Pd(PPh3)4 (22 mg, 0.019 mmol) in DME (2 mL) was sparged with N2 for 5 min. The reaction was sealed and heated to 100° C. for 2 h. The reaction was allowed to cool to rt, poured into EtOAc and partitioned with water. The layers were separated and the organic portion was washed with water, dried (MgSO4), and concentrated. The resulting residue was purified by flash chromatography (SiO2, 100:0-0:100, hexanes-25% MeOH in EtOAc) to afford 102 mg (69% purity) of 4-(4-(6-amino-5-methoxypyridin-3-yl)-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)-N-(2-methoxypyridin-4-yl)pyrimidin-2-amine: LCMS (m/z): 578.5 (MH+), tR=0.74 min.

후처리

  1. customwas sparged with N2 for 5 min
  2. customThe reaction was sealed
  3. temperatureto cool to rt
  4. additionpoured into EtOAc
  5. custompartitioned with water
  6. customThe layers were separated
  7. washthe organic portion was washed with water
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe resulting residue was purified by flash chromatography (SiO2, 100:0-0:100, hexanes-25% MeOH in EtOAc)

출처 및 근거

ORD 기록
ord-b5b59a0ee93d4bb3b9b74b0573aabc03
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865732B2

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