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5-Methyl-2-(tributylstannyl)thiazole → 6-[2-chloro-4-(5-methylthiazol-2-yl)phenyl]-8-ethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 387234
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HRID 387234 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:31](=[O:32])[N:30]([CH2:33][CH3:34])[C:11]3[N:12]=[C:13]([NH:16][C:17]4[CH:22]=[CH:21][C:20]([N:23]5[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]5)=[CH:19][CH:18]=4)[N:14]=[CH:15][C:10]=3[CH:9]=2)=[C:4]([Cl:35])[CH:3]=1.[CH3:36][C:37]1[S:41][C:40]([Sn](CCCC)(CCCC)CCCC)=[N:39][CH:38]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[Cl:35][C:4]1[CH:3]=[C:2]([C:40]2[S:41][C:37]([CH3:36])=[CH:38][N:39]=2)[CH:7]=[CH:6][C:5]=1[C:8]1[C:31](=[O:32])[N:30]([CH2:33][CH3:34])[C:11]2[N:12]=[C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]4)=[CH:19][CH:18]=3)[N:14]=[CH:15][C:10]=2[CH:9]=1
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참가 물질

5

반응물 2

HCID 164271315-Methyl-2-(tributylstannyl)thiazoleHCID 671196306-(4-Bromo-2-chlorophenyl)-8-ethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one

생성물 1

HCID 671196296-[2-chloro-4-(5-methylthiazol-2-yl)phenyl]-8-ethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물
촉매
HCID 1140Toluene용매

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온도
140 °C

실험 절차

6-(4-Bromo-2-chlorophenyl)-8-ethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (12, 194 mg, 0.35 mmol), 5-methyl-2-(tributylstannyl)-thiazole (171 mg, 0.44 mmol), Pd(PPh3)4 (50 mg) and toluene (15 mL) were placed in a microwave tube and oxygen was removed by a stream of argon. The reaction was heated by microwave at 140° C. for 1.5 h and was monitored by LC/MS. The reaction mixture was evaporated and the solid was extracted with chloroform (100 mL). The solids were removed and the filtrate was evaporated and purified by silica gel chromatography (CHCl3+5% MeOH). Yield 17 mg, 0.03 mmol, 8% as yellow solid. LCMS m/z 572 (M+H)+Rt 1.74 min; 1H NMR (400 MHz, CDCl3) δ ppm 8.56 (s, 1H), 8.04 (s, 1H), 7.81-7.83 (d, 1H), 7.54-7.61 (m, 4H), 7.46-7.48 (d, 1H), 7.32-7.37 (s, 1H), 6.97-7.00 (d, 2H), 4.48-4.54 (q, 2H), 3.24-3.26 (m, 4H), 2.63-2.65 (m, 4H), 2.54 (s, 3H), 2.40 (s, 3H), 1.38-1.42 (t, 3H).

후처리

  1. customoxygen was removed by a stream of argon
  2. customThe reaction mixture was evaporated
  3. extractionthe solid was extracted with chloroform (100 mL)
  4. customThe solids were removed
  5. customthe filtrate was evaporated
  6. custompurified by silica gel chromatography (CHCl3+5% MeOH)

출처 및 근거

ORD 기록
ord-02beb93d74eb4707874246702cfe1a1d
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08372970B2

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