Sodium Hydroxide → (2S,4R)-2-(3,5-Bis-trifluoromethyl-phenyl)-N-[3-chloro-6'-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-[2,4']bipyridinyl-3'-yl]-N-methyl-isobutyramide

HRID 547789노트

반응식

HRID 547789 반응식
[Cl:1][C:2]1[C:3](I)=[N:4][CH:5]=[CH:6][CH:7]=1.C([Mg]Cl)(C)C.[F:14][C:15]([F:49])([F:48])[C:16]1[CH:17]=[C:18]([C:26]([CH3:47])([CH3:46])[C:27]([N:29]([C:31]2[CH:32]=[N:33][C:34]([N:38]3[CH2:42][C@H:41]([OH:43])[CH2:40][C@H:39]3[CH2:44][OH:45])=[CH:35][C:36]=2I)[CH3:30])=[O:28])[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1.[OH-].[Na+]>O1CCCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][C:22]([F:23])([F:24])[C:20]1[CH:19]=[C:18]([C:26]([CH3:46])([CH3:47])[C:27]([N:29]([C:31]2[CH:32]=[N:33][C:34]([N:38]3[CH2:42][C@H:41]([OH:43])[CH2:40][C@H:39]3[CH2:44][OH:45])=[CH:35][C:36]=2[C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH3:30])=[O:28])[CH:17]=[C:16]([C:15]([F:49])([F:14])[F:48])[CH:21]=1

참가 물질

8

반응물 4

HCID 14798Sodium HydroxideHCID 108476073-Chloro-2-iodopyridineHCID 86597685HCID 86597685, 화합물HCID 178418918HCID 178418918, 화합물

생성물 1

HCID 86597691(2S,4R)-2-(3,5-Bis-trifluoromethyl-phenyl)-N-[3-chloro-6'-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-[2,4']bipyridinyl-3'-yl]-N-methyl-isobutyramide수율 40%

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매4회

실험 절차

To a solution of 0.500 g (2.09 mmol) 3-chloro-2-iodo-pyridine in 6 ml tetrahydrofuran 1.04 ml (2.09 mmol) of a 2 M solution of isopropylmagnesium chloride in tetrahydrofuran was added dropwise at −40° C. under an atmosphere of argon. After 30 min. 2.3 ml (4.2 mmol) of an anhydrous 1.8 M solution of zinc chloride in tetrahydrofuran was added slowly. The cooling bath was removed after completed addition, and the reaction mixture was stirred at room temperature for 90 min. A portion of 1.6 ml of this solution was added to a solution of 0.15 g (0.24 mmol) (2S,4R)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-iodo-pyridin-3-yl]-N-methyl-isobutyramide and 14 mg (0.012 mmol) tetrakis(triphenylphosphine)palladium(0) in 1 ml tetrahydrofuran. The mixture was heated at 100° C. under microwave irradiation for 30 min. After cooling to room temperature a 0.5 M solution of sodium hydroxide was added, and the mixture was extracted with three portions of dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Flash column chromatography gave 58 mg (40%) of the title compound as a light yellow solid.

후처리

  1. customThe cooling bath was removed
  2. additionaddition
  3. temperatureThe mixture was heated at 100° C. under microwave irradiation for 30 min
  4. additionwas added
  5. extractionthe mixture was extracted with three portions of dichloromethane
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-5f53f01459f1439fa63baa08dca285da
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07939533B2

반응 노트

불러오는 중…