Sodium Bicarbonate → HCID 178480956, 화합물

HRID 432213노트

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HRID 432213 반응식
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[C:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH:36]=[CH:37][CH:38]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>O.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>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:33]3[CH:34]=[C:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:44])([CH3:43])[CH3:45])[CH:36]=[CH:37][CH:38]=3)[C:10]=12

참가 물질

8

반응물 4

HCID 516892Sodium BicarbonateHCID 2735133Sodium Carbonate MonohydrateHCID 2773617tert-Butyl [3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamateHCID 178481014HCID 178481014, 화합물

생성물 1

HCID 178480956HCID 178480956, 화합물수율 81.1%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

A mixture of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1.89 g, 4.28 mmol, 1 equiv), tert-butyl N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (1.64 g, 5.14 mmol, 1.2 equiv), tetrakis(triphenylphosphine)palladium (0.271 g, 0.257 mmol, 0.06 equiv), and sodium carbonate monohydrate (1.28 g, 10.3 mmol, 2.4 equiv) in water (13 mL) and DME (18 mL) was heated at 85° C. for 14 h. The mixture was allowed to cool to ambient temperature. Saturated aqueous sodium bicarbonate solution (15 mL) was added and the aqueous portion was extracted with EtOAc (30 mL). The organic extract was dried over MgSO4, filtered, and concentrated to afford a pale yellow solid. Purification by column chromatography on silica gel (elution with 2 L of 95:4:1 CH2Cl2:Et3N:MeOH) afforded cis-tert-butyl N-(3-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)carbamate as a white solid (1.76 g, 3.47 mmol): 1H NMR (d6 DMSO, 400 MHz): δ H 9.55 (1H, s), 8.23 (1H, s), 7.81 (1H, s), 7.40-7.52 (2H, m), 7.24 (1H, d, J=7.5 Hz), 4.79-4.81 (1H, m), 2.05-2.44 (11H, m), 2.14 (3H, s), 1.54-1.70 (6H, m), 1.49 (9H, s); RP-HPLC (Delta Pak C18, 5 μm, 300 Å, 15cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 12.61 min.

후처리

  1. temperatureto cool to ambient temperature
  2. extractionthe aqueous portion was extracted with EtOAc (30 mL)
  3. extractionThe organic extract
  4. dry with materialwas dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a pale yellow solid
  8. customPurification by column chromatography on silica gel (elution with 2 L of 95:4:1 CH2Cl2:Et3N:MeOH)

출처 및 근거

ORD 기록
ord-f064009983554f0face2bbdf0e128b0f
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06660744B1

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