Cesium carbonate → 2,6-Dichloro-4-Cyano-N-{2-[(Cyclopropylcarbonyl)amino]pyridin-4-Yl}benzamide

HRID 449916

반응식

HRID 449916 반응식
Br[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:20])[C:10]2[C:15]([Cl:16])=[CH:14][C:13]([C:17]#[N:18])=[CH:12][C:11]=2[Cl:19])[CH:5]=[CH:4][N:3]=1.[CH:21]1([C:24]([NH2:26])=[O:25])[CH2:23][CH2:22]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:19][C:11]1[CH:12]=[C:13]([C:17]#[N:18])[CH:14]=[C:15]([Cl:16])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:26][C:24]([CH:21]2[CH2:23][CH2:22]2)=[O:25])[CH:7]=1)=[O:20]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86648954N-(2-bromopyridin-4-yl)-2,6-dichloro-4-cyanobenzamide

생성물 1

HCID 596182732,6-Dichloro-4-Cyano-N-{2-[(Cyclopropylcarbonyl)amino]pyridin-4-Yl}benzamide수율 40%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
140 °C

실험 절차

A mixture of N-(2-bromopyridin-4-yl)-2,6-dichloro-4-cyanobenzamide (74 mg, 0.20 mmol), cyclopropanecarboxamide (34 mg, 0.40 mmol), Pd2(dba)3 (18 mg, 0.020 mmol), Xantphos (23 mg, 0.040 mmol), Cs2CO3 (131 mg, 0.40 mmol), dioxane (1.2 mL) was heated to 140° C. for 1 hour in a microwave reactor under nitrogen atmosphere. The mixture was filtered through Celite and then conentrated under reduced pressure. The residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford the desired product (30 mg, yield: 40%). 1H NMR (500 MHz, DMSO-d6): δ 11.28 (s, 1H), 10.79 (s, 1H), 8.36-8.24 (m, 4H), 7.47 (m, 1H), 2.00 (m, 1H), 0.81-0.79 (m, 4H). LCMS (ESI) m/z: 375 [M+H+].

후처리

  1. filtrationThe mixture was filtered through Celite
  2. customThe residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

출처 및 근거

ORD 기록
ord-98de4c594b144a25a334c763f4709939
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486950B2

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