Water → (R)-4-(1-(4-cyclopropoxy-6-(2-cyclopropylethynyl)pyrido[3,2-d]pyrimidin-2-ylamino)ethyl)benzenesulfonamide

HRID 42367

반응식

HRID 42367 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[C:7]([NH:16][CH:17]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([NH2:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[CH3:18])[N:8]=[C:9]([O:12][CH:13]3[CH2:15][CH2:14]3)[C:10]=2[N:11]=1.[C:29]([CH:31]1[CH2:33][CH2:32]1)#[CH:30].O>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH:13]1([O:12][C:9]2[C:10]3[N:11]=[C:2]([C:30]#[C:29][CH:31]4[CH2:33][CH2:32]4)[CH:3]=[CH:4][C:5]=3[N:6]=[C:7]([NH:16][C@@H:17]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([NH2:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[CH3:18])[N:8]=2)[CH2:15][CH2:14]1

참가 물질

7

반응물 3

HCID 962WaterHCID 138823CyclopropylacetyleneHCID 767384494-[1-(6-Chloro-4-cyclopropoxy-pyrido[3,2-d]pyrimidin-2-ylamino)-ethyl]-benzenesulfonamide

생성물 1

HCID 58275408(R)-4-(1-(4-cyclopropoxy-6-(2-cyclopropylethynyl)pyrido[3,2-d]pyrimidin-2-ylamino)ethyl)benzenesulfonamide수율 77.7%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

A mixture of 4-[1-(6-Chloro-4-cyclopropoxy-pyrido[3,2-d]pyrimidin-2-ylamino)-ethyl]-benzenesulfonamide (300 mg, 0.71 mmol), PdCl2(PPh3)2 (25 mg, 0.035 mmol), CuI (13.5 mg, 0.07 mmol) in TEA (1 mL) and DMF (5 mL) was degassed for 10 min then purged with argon. Ethynyl-cyclopropane (0.3 mL, 3.5 mmol) was added and the reaction tube was sealed and heated at 80° C. for 3 hours. After cooling to room temperature, the reaction mixture was poured into water and extracted twice with EtOAc. The combined organic layers were washed with 5% LiCl solution and brine. Solvent was removed by concentration in vacuo and the residue was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, to provide 248 mg (62%) of desired product. MS (m/z) 450.0 [M+H]+; HPLC Rt=2.16 min.

후처리

  1. customwas degassed for 10 min
  2. customthen purged with argon
  3. customthe reaction tube was sealed
  4. temperatureAfter cooling to room temperature
  5. extractionextracted twice with EtOAc
  6. washThe combined organic layers were washed with 5% LiCl solution and brine
  7. customSolvent was removed by concentration in vacuo
  8. customthe residue was purified by RP HPLC

출처 및 근거

ORD 기록
ord-675049cfd59f4a7eba02f6414bc4cfb3
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536187B2

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