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

HRID 1182964ノート

反応式

HRID 1182964 の反応式
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

参加物

5

反応物 3

HCID 516892Sodium BicarbonateHCID 52936632N-[5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]benzenesulfonamide2 回HCID 86671067Tert-butyl 4-(6-chloropyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate

生成物 1

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

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a9b574b67e7d41259292537c2c648a6c
出典データセット
uspto-grants-2014_03
特許番号
US08664230B2

反応ノート

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