Sodium Bicarbonate → N-(2-chloro-5-(4-(6-methoxypyridin-3-ylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide

HRID 1182980ノート

反応式

HRID 1182980 の反応式
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:12][C:13]3[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=3)[C:10]=2[N:11]=1.[Cl:21][C:22]1[C:27]([NH:28][S:29]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[F:39])(=[O:31])=[O:30])=[CH:26][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][N:23]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:21][C:22]1[C:27]([NH:28][S:29]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[F:39])(=[O:31])=[O:30])=[CH:26][C:25]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:12][C:13]4[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=4)[C:10]=3[N:11]=2)=[CH:24][N:23]=1

参加物

5

反応物 3

HCID 516892Sodium BicarbonateHCID 866710776-chloro-N-(6-methoxy-3-pyridinyl)-Pyrido[3,2-d]pyrimidin-4-amine2 回HCID 86671080N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide2 回

生成物 1

HCID 66558474N-(2-chloro-5-(4-(6-methoxypyridin-3-ylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide収率 31.1%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 6-chloro-N-(6-methoxypyridin-3-yl)pyrido[3,2-d]pyrimidin-4-amine (Intermediate 22) (0.040 g, 0.139 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-yl)-2,4-difluorobenzenesulfonamide (Intermediate 3) (0.066 g, 0.153 mmol), PdCl2(dppf)-CH2Cl2Adduct (0.011 g, 0.014 mmol) and 1 N aq. sodium bicarbonate (0.278 ml, 0.278 mmol) in dioxane (1.40 ml) subjected to microwave irradiation for 1 hour at 110° C. After cooling to room temperature, the reaction mixture was filtered through Celite and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give N-(2-chloro-5-(4-(6-methoxypyridin-3-ylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.024 g, 31%) as a yellow solid. 1H-NMR (DMSO-d6, Varian 400 MHz) δ 3.89 (3H, s), 6.94 (3H, s), 6.89-7.05 (1H, d, J=8.4 Hz), 7.17-7.28 (1H, m), 7.50-7.65 (1H, m), 7.74-7.86 (1H, m), 8.17 (1H, dd, J=2.4, 8.8 Hz), 8.33 (1H, d, J=8.8 Hz), 8.36 (1H, d, J=8.8 Hz), 8.57 (1H, d, J=8.8 Hz), 8.62 (2H, s), 8.82 (1H, s), 9.48 (1H, s), 10.33 (1H, s), 10.98 (1H, br s). m/z=556.2 [M+1]+.

後処理

  1. customirradiation for 1 hour at 110° C
  2. filtrationthe reaction mixture was filtered through Celite
  3. washwashed with CH2Cl2
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)

出典と根拠

ORDレコード
ord-b6e841ec48a54e1a91ab151f2416b8f3
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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