Acetic Anhydride → (S)-2-(4-(3-(tert-butoxy)-2-(4-(tert-butyl)benzamido)-3-oxopropyl)phenyl)pyrimidine-5-carboxylic acid

HRID 1775861노트

반응식

HRID 1775861 반응식
[CH:1]([O-:3])=[O:2].[Li+].CCN(C(C)C)C(C)C.C(OC(=O)C)(=O)C.Br[C:22]1[CH:23]=[N:24][C:25]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C@H:35]([NH:43][C:44](=[O:55])[C:45]3[CH:50]=[CH:49][C:48]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:47][CH:46]=3)[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:30][CH:29]=2)=[N:26][CH:27]=1>CN(C=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:39]([O:38][C:36](=[O:37])[C@@H:35]([NH:43][C:44](=[O:55])[C:45]1[CH:50]=[CH:49][C:48]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:47][CH:46]=1)[CH2:34][C:31]1[CH:32]=[CH:33][C:28]([C:25]2[N:24]=[CH:23][C:22]([C:1]([OH:3])=[O:2])=[CH:27][N:26]=2)=[CH:29][CH:30]=1)([CH3:42])([CH3:41])[CH3:40]

참가 물질

8

반응물 4

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 23680280Lithium formateHCID 86689676tert-butyl (S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate

생성물 1

HCID 117740712(S)-2-(4-(3-(tert-butoxy)-2-(4-(tert-butyl)benzamido)-3-oxopropyl)phenyl)pyrimidine-5-carboxylic acid수율 88%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 311Citric Acid용매HCID 6228Dimethylformamide용매2회

반응 조건

온도
120 °C

실험 절차

Prepared using General Procedure 10. Into an oven-dried vial containing lithium formate (58 mg (1.1 mmol) in DMF (5 mL) were added DIEA (400 μL, 2.2 mmol) and acetic anhydride (210 μL, 2.2 mmol). After stirring for 1 h, the reaction mixture was degassed by N2 bubbling. A second, degassed solution containing (S)-tert-butyl 3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate, INT-14 (200 mg, 0.4 mmol) and PdCl2(dppf) (27 mg, 0.04 mmol) in DMF (5 mL) was added via cannula. The resulting mixture was heated for 1 h at 120° C. in a microwave reactor. The reaction mixture was diluted with 10% citric acid and extracted with EA. The organic extract was dried (Na2SO4), concentrated, and purified by chromatography (EA/hexane) to provide 166 mg (88%) of (S)-2-(4-(3-(tert-butoxy)-2-(4-(tert-butyl)benzamido)-3-oxopropyl)phenyl)pyrimidine-5-carboxylic acid as a brown solid. LCMS-ESI (m/z) calculated for C29H33BN3O5: 503.6. found 504.2 [M+H]+, tR=3.87 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 9.24 (s, 2H), 8.42 (d, J=8.2 Hz, 2H), 7.75 (t, J=11.9 Hz, 2H), 7.45 (d, J=8.4 Hz, 2H), 7.34 (d, J=8.2 Hz, 2H), 6.91 (t, J=11.5 Hz, 1H), 5.12 (dd, J=12.9, 5.5 Hz, 1H), 3.32 (qd, J=13.8, 5.4 Hz, 2H), 1.50 (s, 9H), 1.29 (d, J=29.8 Hz, 9H).

후처리

  1. customPrepared
  2. customthe reaction mixture was degassed by N2 bubbling
  3. customA second, degassed solution
  4. additionwas added via cannula
  5. extractionextracted with EA
  6. extractionThe organic extract
  7. dry with materialwas dried (Na2SO4)
  8. concentrationconcentrated
  9. custompurified by chromatography (EA/hexane)

출처 및 근거

ORD 기록
ord-1426e87d89404076a74763172502636f
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09260427B2

반응 노트

불러오는 중…