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

HRID 1485568ノート

反応式

HRID 1485568 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][CH:13]3[CH2:15][CH2:14]3)[C:10]=2[N:11]=1.[Cl:16][C:17]1[C:22]([NH:23][S:24]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[F:34])(=[O:26])=[O:25])=[CH:21][C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][N:18]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:16][C:17]1[C:22]([NH:23][S:24]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=2[F:34])(=[O:26])=[O:25])=[CH:21][C:20]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[CH:7][N:8]=[C:9]([NH:12][CH:13]4[CH2:15][CH2:14]4)[C:10]=3[N:11]=2)=[CH:19][N:18]=1

参加物

6

反応物 3

HCID 516892Sodium BicarbonateHCID 866710756-chloro-N-cyclopropylpyrido[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 66558472N-(2-chloro-5-(4-(cyclopropylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide収率 53%

試薬・触媒・溶媒 2

HCID 178418807HCID 178418807、化合物触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of 6-chloro-N-cyclopropylpyrido[3,2-d]pyrimidin-4-amine (Intermediate 20) (0.060 g, 0.272 mmol), N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-yl)-2,4-difluorobenzenesulfonamide (Intermediate 3) (0.141 g, 0.326 mmol), PdCl2(dppf)-CH2Cl2 Adduct (2.221 mg, 2.72 μmol) and 1 N aq. sodium bicarbonate (0.544 ml, 0.544 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-(cyclopropylamino)pyrido[3,2-d]pyrimidin-6-yl) pyridin-3-yl)-2,4-difluorobenzenesulfonamide (0.070 g, 53%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 0.78-0.82 (2H, m), 1.04-1.09 (2H, m), 3.08-3.13 (1H, m), 6.95-7.02 (2H, m), 7.30 (1H, brs), 7.85-7.91 (1H, m), 8.08 (1H, d, J=8.8 Hz), 8.24 (1H, d, J=8.8 Hz), 8.67 (1H, d, J=2.0 Hz), 8.76 (1H, s), 8.81 (1H, d, J=2.0 Hz). m/z=489.2 [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-e1b00fda09e14d8c875323aa406cddbb
出典データセット
uspto-grants-2016_08
特許番号
US09422298B2

反応ノート

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