Sodium Bicarbonate → Tert-butyl 4-(6-(5-(phenylsulfonamido)-pyridine-3-yl)pyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate

HRID 1182964노트

반응식

HRID 1182964 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([O:12][CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[C:10]=2[N:11]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([NH:40][S:41]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)(=[O:43])=[O:42])[CH:37]=[N:38][CH:39]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[C:44]1([S:41]([NH:40][C:36]2[CH:35]=[C:34]([C:2]3[CH:3]=[CH:4][C:5]4[N:6]=[CH:7][N:8]=[C:9]([O:12][CH:13]5[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]5)[C:10]=4[N:11]=3)[CH:39]=[N:38][CH:37]=2)(=[O:43])=[O:42])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

참가 물질

5

반응물 3

HCID 516892Sodium BicarbonateHCID 52936632N-[5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]benzenesulfonamide2회HCID 86671067Tert-butyl 4-(6-chloropyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate

생성물 1

HCID 66558111Tert-butyl 4-(6-(5-(phenylsulfonamido)-pyridine-3-yl)pyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate수율 32.4%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

A mixture of tert-butyl 4-(6-chloropyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate (0.3 g, 0.822 mmol), N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzene-sulfonamide (Intermediate 2) (0.355 g, 0.987 mmol), PdCl2(dppf)-CH2Cl2Adduct (0.067 g, 0.082 mmol) and 1N aq. sodium bicarbonate (1.64 ml, 1.64 mmol) in dioxane (4.11 ml) was subjected to microwave irradiation for 30 min at 120° C., and cooled to room temperature. The reaction mixture was filtered through a Celite pad and washed with EtOAc. The filtrate was diluted water and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give tert-butyl 4-(6-(5-(phenylsulfonamido)-pyridine-3-yl)pyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate (0.15 g, 32%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.49 (9H, s), 1.95-2.05 (2H, m), 2.14-2.18 (2H, m), 3.36-3.43 (2H, m), 3.89-3.95 (2H, m), 5.63-5.37 (1H, m), 7.46-7.52 (2H, m), 7.56-7.60 (1H, m), 7.85 (1H, d, J=7.2 Hz), 8.21 (1H, d, J=8.8 Hz), 8.34 (1H, s), 8.37 (1H, d, J=2.4 Hz), 8.41 (1H, d, J=2.0 Hz), 8.83 (1H, s), 9.14 (1H, d, J=1.6 Hz).

후처리

  1. customirradiation for 30 min at 120° C.
  2. filtrationThe reaction mixture was filtered through a Celite pad
  3. washwashed with EtOAc
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)

출처 및 근거

ORD 기록
ord-a9b574b67e7d41259292537c2c648a6c
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08664230B2

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