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Thioglycolic Acid → (R)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80810
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HRID 80810 반응식
[CH:1]([C:4]1[CH:8]=[C:7]([N:9]2[CH2:57][CH2:56][C:12]3[N:13]=[C:14]([C:36]4[CH:44]=[CH:43][CH:42]=[C:41]5[C:37]=4[C:38]([CH3:55])=[CH:39][N:40]5[S:45]([C:48]4[CH:54]=[CH:53][C:51]([CH3:52])=[CH:50][CH:49]=4)(=[O:47])=[O:46])[N:15]=[C:16]([N:17]4[CH2:22][CH2:21][N:20](S(C5C=CC=CC=5[N+]([O-])=O)(=O)=O)[C@H:19]([CH3:35])[CH2:18]4)[C:11]=3[CH2:10]2)[N:6]([CH3:58])[N:5]=1)([CH3:3])[CH3:2].C1CCN2C(=NCCC2)CC1.SCC(O)=O>CN(C=O)C.O.ClCCl>[CH:1]([C:4]1[CH:8]=[C:7]([N:9]2[CH2:57][CH2:56][C:12]3[N:13]=[C:14]([C:36]4[CH:44]=[CH:43][CH:42]=[C:41]5[C:37]=4[C:38]([CH3:55])=[CH:39][N:40]5[S:45]([C:48]4[CH:49]=[CH:50][C:51]([CH3:52])=[CH:53][CH:54]=4)(=[O:46])=[O:47])[N:15]=[C:16]([N:17]4[CH2:22][CH2:21][NH:20][C@H:19]([CH3:35])[CH2:18]4)[C:11]=3[CH2:10]2)[N:6]([CH3:58])[N:5]=1)([CH3:2])[CH3:3]
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참가 물질

7

반응물 3

HCID 1133Thioglycolic AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 71240484HCID 71240484, 화합물

생성물 1

HCID 71240581(R)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

시약·촉매·용매 3

HCID 962Water
용매
HCID 6228Dimethylformamide용매
HCID 6344Dichloromethane용매

실험 절차

To a solution of (R)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (105 mg, 0.127 mmol) in DMF (3 mL) was added DBU (0.1 mL, 0.64 mmol) followed by 2-mercaptoacetic acid (0.018 mL, 0.255 mmol). The mixture was stirred for 3 hours and then diluted with water and dichloromethane. The layers were separated and the aqueous layer was extracted three additional times with dichloromethane. The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting residue was purified via silica gel flash chromatography [4-25% (2 M NH3 in MeOH)/DCM] to provide (R)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. MS (ESI+) m/z 639.4 (M+H)+.

후처리

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted three additional times with dichloromethane
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified via silica gel flash chromatography [4-25% (2 M NH3 in MeOH)/DCM]

출처 및 근거

ORD 기록
ord-df0755466f0540289aa0b3a87923e88c
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08846656B2

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