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

HRID 1485568노트

반응식

HRID 1485568 반응식
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

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 866710756-chloro-N-cyclopropylpyrido[3,2-d]pyrimidin-4-amine2회HCID 86671080N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide2회

생성물 1

HCID 66558472N-(2-chloro-5-(4-(cyclopropylamino)pyrido[3,2-d]pyrimidin-6-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide수율 53%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-e1b00fda09e14d8c875323aa406cddbb
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422298B2

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