Trifluoroacetic acid → 4-[4-(2-Methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester

HRID 1931638

反応式

HRID 1931638 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([O:23][C:24]4[C:25]([CH3:35])=[N:26][C:27]([N:30]5[CH:34]=[N:33][CH:32]=[N:31]5)=[CH:28][CH:29]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])(C)([CH3:3])[CH3:2].FC(F)(F)C(O)=O.ClC(OC(C)C)=O.C(N(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([O:23][C:24]4[C:25]([CH3:35])=[N:26][C:27]([N:30]5[CH:34]=[N:33][CH:32]=[N:31]5)=[CH:28][CH:29]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:12][CH2:13]1)=[O:7])([CH3:3])[CH3:2]

参加物

7

反応物 5

HCID 6422Trifluoroacetic acidHCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 445146854-[4-(2-Methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yloxy)pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 445144004-[4-(2-Methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester収率 72%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A mixture of 4-[4-(2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Example 101; 50 mg, 0.105 mmol), trifluoroacetic acid (428 μL) and dichloromethane (2 mL) was stirred at room temperature for 30 min. The volatiles were evaporated under high vacuum and the residue was dissolved in dichloromethane (3 mL). Isopropyl chloroformate (1 M in toluene; 158 μL, 0.16 mmol) and triethylamine (95 μL, 0.68 mmol) were added and the mixture was stirred overnight at room temperature. 1 M aqueous sodium carbonate (6 mL) and dichloromethane (3 mL) were added, and the aqueous layer was extracted twice with dichloromethane. The combined organic extracts were evaporated and the residue was purified by preparative C18 HPLC, eluting with 10-100% acetonitrile/water. Samples containing the product were extracted three times with dichloromethane and the solvent was evaporated to give 4-[4-(2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid isopropyl ester (35 mg, 72%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.28 (d, 6H, J=6.0 Hz), 1.97-2.10 (m, 2H, J=10.9 Hz), 2.20-2.35 (m, 2H), 2.46 (s, 3H), 2.89-3.14 (m, 2H), 4.32-4.48 (m, 2H), 4.84-5.08 (m, 2H), 7.68 (d, 1H, J=8.8 Hz), 7.86 (d, 1H, J=8.8 Hz), 8.11 (s, 1H), 8.17 (s, 1H), 8.48 (s, 1H), 9.19 (s, 1H). Mass spectrum (ES) MH+=464. HRMS Calcd. for C22H26N9O3 (MH+): 464.2153. Found: 464.2151.

後処理

  1. customThe volatiles were evaporated under high vacuum
  2. dissolutionthe residue was dissolved in dichloromethane (3 mL)
  3. stirringthe mixture was stirred overnight at room temperature
  4. extractionthe aqueous layer was extracted twice with dichloromethane
  5. customThe combined organic extracts were evaporated
  6. customthe residue was purified by preparative C18 HPLC
  7. washeluting with 10-100% acetonitrile/water
  8. additionSamples containing the product
  9. extractionwere extracted three times with dichloromethane
  10. customthe solvent was evaporated

出典と根拠

ORDレコード
ord-459fee83697143a3ab81acba48d4b3d7
出典データセット
uspto-grants-2012_05
特許番号
US08188098B2

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