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 2279599ノート

反応式

HRID 2279599 の反応式
[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]

参加物

8

反応物 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

生成物 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-carboxamide収率 48.4%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-c20cbbe63f2f4323aa8443875fdad38f
出典データセット
uspto-grants-2015_09
特許番号
US09133187B2

反応ノート

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