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Dimethylamine → 1-[3-(1-{[tert-Butyl(diphenyl)silyl]oxy}-2-methylpropan-2-yl)-1-{3-[2-(dimethylamino)ethoxy]phenyl}-1H-pyrazol-5-yl]-3-[(1S,4R)-4-({3-[(2S)-2-methylpiperidin-1-yl][1,2,4]triazolo[4,3-a]pyridin-6-yl}oxy)-1,2,3,4-tetrahydronaphthalen-1-yl]urea

HRID 2282738
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HRID 2282738 반응식
CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N:15]2[C:19]([NH:20][C:21](=[O:50])[NH:22][C@@H:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[C@H:26]([O:33][C:34]4[CH:35]=[CH:36][C:37]5[N:38]([C:40]([N:43]6[CH2:48][CH2:47][CH2:46][CH2:45][C@@H:44]6[CH3:49])=[N:41][N:42]=5)[CH:39]=4)[CH2:25][CH2:24]3)=[CH:18][C:17]([C:51]([CH3:72])([CH3:71])[CH2:52][O:53][Si:54]([C:67]([CH3:70])([CH3:69])[CH3:68])([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=3)=[N:16]2)[CH:10]=1)(=O)=O.[CH3:73][NH:74][CH3:75]>C1COCC1>[Si:54]([O:53][CH2:52][C:51]([C:17]1[CH:18]=[C:19]([NH:20][C:21]([NH:22][C@@H:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C@H:26]([O:33][C:34]3[CH:35]=[CH:36][C:37]4[N:38]([C:40]([N:43]5[CH2:48][CH2:47][CH2:46][CH2:45][C@@H:44]5[CH3:49])=[N:41][N:42]=4)[CH:39]=3)[CH2:25][CH2:24]2)=[O:50])[N:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:7][CH2:6][N:74]([CH3:75])[CH3:73])[CH:10]=2)[N:16]=1)([CH3:71])[CH3:72])([C:67]([CH3:68])([CH3:69])[CH3:70])([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1
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4

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HCID 674DimethylamineHCID 866872892-{3-[3-(1-{[tert-Butyl(diphenyl)silyl]oxy}-2-methylpropan-2-yl)-5-({[(1S,4R)-4-({3-[(2S)-2-methylpiperidin-1-yl][1,2,4]triazolo[4,3-a]pyridin-6-yl}oxy)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl}amino)-1H-pyrazol-1-yl]phenoxy}ethyl methanesulfonate

생성물 1

HCID 866872911-[3-(1-{[tert-Butyl(diphenyl)silyl]oxy}-2-methylpropan-2-yl)-1-{3-[2-(dimethylamino)ethoxy]phenyl}-1H-pyrazol-5-yl]-3-[(1S,4R)-4-({3-[(2S)-2-methylpiperidin-1-yl][1,2,4]triazolo[4,3-a]pyridin-6-yl}oxy)-1,2,3,4-tetrahydronaphthalen-1-yl]urea
수율 75%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
60 °C

실험 절차

A solution of Intermediate 153i (131 mg, 0.13 mmol) in THF (0.8 mL) was treated with a 2M solution of dimethylamine in THF (1.3 mL, 2.6 mmol) and the mixture was stirred at 60° C. for 18 h. The cooled solution was concentrated in vacuo, and the residue was partitioned between DCM and water. The phases were separated and the aqueous layer was extracted with DCM (×2). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo to a brown gum. The gum was purified by FCC, using 0-8% (2N NH3/MeOH) in DCM, to give the title compound as a white foam (93 mg, 75%). LCMS (Method 3): Rt 3.91 min, m/z 960.6 [MH+].

후처리

  1. concentrationThe cooled solution was concentrated in vacuo
  2. customthe residue was partitioned between DCM and water
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with DCM (×2)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo to a brown gum
  8. customThe gum was purified by FCC

출처 및 근거

ORD 기록
ord-aaed9db65640483e979b1e2bbf5a500d
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09139584B2

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