Sodium Carbonate → 2-(2-(1-Aminoisoquinolin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol

HRID 1945731노트

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HRID 1945731 반응식
Cl[C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[S:10][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[CH:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([NH2:39])=[N:31][CH:30]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:39][C:32]1[C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:29]([C:2]2[N:3]=[C:4]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[C:5]3[S:10][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[CH:8][C:6]=3[N:7]=2)=[CH:30][N:31]=1

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 461807242-(2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-olHCID 674926724-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-amine

생성물 1

HCID 596061952-(2-(1-Aminoisoquinolin-4-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol수율 6%

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 6342Acetonitrile용매

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온도
140 °C

실험 절차

To a solution of 2-(2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol (63 mg, 0.20 mmol) in acetonitrile (3.6 ml) in a microwave reaction vessel was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-amine (110 mg, 0.40 mmol), Bis(triphenylphosphine)palladium(II) chloride (7.02 mg, 0.010 mmol) and 1M sodium carbonate in water (0.60 ml). The reaction vessel was sealed and heated in the microwave at 140° C. for 20 minutes. LC-MS of the reaction mixture showed no more starting material. The solvent was evaporated and the resulting oil was purified on silica gel (0 to 20% of 2N NH3 in MeOH/DCM). The resulting oil was further purified by reversed phase HPLC to give 141 as an off-white solid (4.7 mg, 6%) 1H NMR (DMSO d6, 400 MHz) 9.02 (d, 1H, J=8.4 Hz), 8.26 (s, 1H), 8.26 (d, 1H, J=8.4 Hz), 7.67 (t, 1H, J=7.6 Hz), 7.50 (t, 1H, J=7.6)m 7.33 (s, 1H), 7.11 (s, 2H), 5.84 (s, 1H), 3.98-3.94 (m, 4H), 3.81-3.78 (m, 4H), 1.61 (m, 6H). LCMS m/z: 422 (MH+)

후처리

  1. customThe reaction vessel was sealed
  2. customThe solvent was evaporated
  3. customthe resulting oil was purified on silica gel (0 to 20% of 2N NH3 in MeOH/DCM)
  4. customThe resulting oil was further purified by reversed phase HPLC

출처 및 근거

ORD 기록
ord-93c7c03d0748416c8e3ef4beb1427986
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08394796B2

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