Sodium Carbonate → 5-(8,8-Dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluoren-3-yl)-pyrimidin-2-ylamine

HRID 334179노트

반응식

HRID 334179 반응식
Cl[C:2]1[N:3]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:5]2[CH:6]=[C:7]3[N:12]([C:13]=2[N:14]=1)[CH2:11][CH2:10][O:9][C:8]3([CH3:16])[CH3:15].CC1(C)C(C)(C)OB([C:31]2[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:15][C:8]1([CH3:16])[C:7]2[N:12]([C:13]3[N:14]=[C:2]([C:31]4[CH:32]=[N:33][C:34]([NH2:37])=[N:35][CH:36]=4)[N:3]=[C:4]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:5]=3[CH:6]=2)[CH2:11][CH2:10][O:9]1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 866673893-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene

생성물 1

HCID 573839575-(8,8-Dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluoren-3-yl)-pyrimidin-2-ylamine수율 15%

시약·촉매·용매 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매HCID 6342Acetonitrile용매

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온도
150 °C

실험 절차

A mixture of 3-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,6-dihydro-8H-7-oxa-2,4,4b-triaza-fluorene (75 mg, 0.23 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine (115 mg, 0.52 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)-phosphine)dichloropalladium(II) (25 mg, 0.035 mmol) and sodium carbonate (1 mL, 1.0 mmol, 1M aqueous solution) in acetonitrile (3 mL) was degassed and heated at 150° C. for 30 mins in a microwave reactor, then concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0 to 75% ethyl acetate in cyclohexane) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 5-98%) affording 177 as a off-white solid (13 mg, 15%). LCMS (method B): RT=3.50 min, [M+H]+=382. 1H NMR (400 MHz, CDCl3): δ 9.27 (2H, s), 6.12 (1H, s), 5.27 (2H, broad s), 4.21 (2H, m), 4.14 m), 3.88 (4H, m), 1.62 (6H, s)

후처리

  1. customwas degassed
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (SiO2, gradient 0 to 75% ethyl acetate in cyclohexane)

출처 및 근거

ORD 기록
ord-92f27845235e4feab6196c8d4a73a22d
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883799B2

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