Sodium Carbonate → (R)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxamide

HRID 2279599노트

반응식

HRID 2279599 반응식
[O:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[N:9]=[CH:10][C:11]3[CH2:17][CH2:16][C@H:15]([C:18]([OH:20])=O)[O:14][C:12]=3[N:13]=2)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Si:45]([O:52][CH2:53][C@H:54]([C:56]1[CH:61]=[CH:60][C:59]([Cl:62])=[C:58]([F:63])[CH:57]=1)[NH2:55])([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46].CCN(C(C)C)C(C)C.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C(Cl)Cl>[Si:45]([O:52][CH2:53][C@@H:54]([NH:55][C:18]([C@@H:15]1[O:14][C:12]2[N:13]=[C:8]([NH:7][CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)[N:9]=[CH:10][C:11]=2[CH2:17][CH2:16]1)=[O:20])[C:56]1[CH:61]=[CH:60][C:59]([Cl:62])=[C:58]([F:63])[CH:57]=1)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46]

참가 물질

8

반응물 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86705474(S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethanamineHCID 86705581(R)-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxylic acid

생성물 1

HCID 86705582(R)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxamide수율 48.4%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

A vial was charged 408 (0.050 g, 0.15 mmol), HATU (0.069 g, 0.18 mmol), 68 (0.055 g, 0.18 mmol), DIPEA (1 mL), DCM (2 mL) and DMF (1 mL) and stirred for 18 h. To the solution was added satd. aq. Na2CO3 (5 mL), and the mixture stirred for 5 min. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography (SNAP 25) eluting with DCM/MeOH (95:5) to afford 0.041 g (43%) of (R)—N—((S)-2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-2-(tetrahydro-2H-pyran-4-ylamino)-6,7-dihydro-5H-pyrano[2,3-d]pyrimidine-7-carboxamide (410): MS m/z (APCI-pos) M+1=565.0.

후처리

  1. additionTo the solution was added satd
  2. washThe organic phase was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by SiO2 chromatography (SNAP 25)
  7. washeluting with DCM/MeOH (95:5)

출처 및 근거

ORD 기록
ord-c20cbbe63f2f4323aa8443875fdad38f
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133187B2

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