Potassium Carbonate → (3R)-N-[4'-(Hydroxymethyl)-3'-fluoro-1,1'-biphenyl-4-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide

HRID 722193노트

반응식

HRID 722193 반응식
B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][OH:33])=[C:28]([F:34])[CH:27]=1.Br[C:36]1[CH:41]=[CH:40][C:39]([NH:42][C:43]([C@@H:45]2[CH:50]3[CH2:51][CH2:52][N:47]([CH2:48][CH2:49]3)[CH2:46]2)=[O:44])=[CH:38][CH:37]=1.[OH-].[Na+]>CN(C=O)C.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]>[OH:33][CH2:32][C:29]1[CH:30]=[CH:31][C:26]([C:36]2[CH:41]=[CH:40][C:39]([NH:42][C:43]([C@@H:45]3[CH:50]4[CH2:51][CH2:52][N:47]([CH2:48][CH2:49]4)[CH2:46]3)=[O:44])=[CH:38][CH:37]=2)=[CH:27][C:28]=1[F:34]

참가 물질

8

반응물 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 2733548Bis(pinacolato)diboraneHCID 2734027(4-Bromo-2-fluorophenyl)methanolHCID 58742393(3R)-N-(4-bromophenyl)-1-azabicyclo[2.2.2]octane-3-carboxamide

생성물 1

HCID 58742400(3R)-N-[4'-(Hydroxymethyl)-3'-fluoro-1,1'-biphenyl-4-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 6228Dimethylformamide용매

반응 조건

온도
85 °C

실험 절차

492 mg (1.62) of bis(pinacolato)diboron, 804 mg (5.82 mmol) of dry potassium carbonate, and 398 mg (1.94 mmol) of (4-bromo-2-fluorophenyl)methanol are dissolved in 4.2 ml of DMF. Argon is passed through the reaction mixture for 15 minutes, and then 59 mg (0.08 mmol) of PdCl2(dppf) are added, and the mixture is heated at 85° C. overnight. Then, 500 mg (1.62 mmol) of (3R)-N-(4-bromophenyl)-1-azabicyclo[2.2.2]octane-3-carboxamide, 8.1 ml of 1N sodium hydroxide solution and a further 59 mg (0.02 mmol) of PdCl2(dppf) are added. The mixture is heated at 85° C. overnight. The solvent is removed under reduced pressure. The crude product is purified by preparative HPLC. 21 mg (3% of theory) of the title compound are obtained.

후처리

  1. temperatureThe mixture is heated at 85° C. overnight
  2. customThe solvent is removed under reduced pressure
  3. customThe crude product is purified by preparative HPLC

출처 및 근거

ORD 기록
ord-f2b2e38ec9ee40f9b1f25029cf5227c9
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07138410B2

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