Diisopropylethylamine → 5-cyano-N-((1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutyl)pyridine-2-sulfonamide

HRID 1854329노트

반응식

HRID 1854329 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][C@@H:12]2[CH2:15][C@H:14]([C:16]3[N:20]4[C:21]5[CH:27]=[CH:26][N:25]([S:28]([C:31]6[CH:37]=[CH:36][C:34]([CH3:35])=[CH:33][CH:32]=6)(=[O:30])=[O:29])[C:22]=5[N:23]=[CH:24][C:19]4=[N:18][N:17]=3)[C:13]2([CH3:39])[CH3:38])(=[O:10])=[O:9])=[N:6][CH:7]=1.[C:40]([NH:43][C@@H]1C[C@H](C(O)=O)C1(C)C)(=O)C.CCN(C(C)C)C(C)C.BrC1C=CC(S(Cl)(=O)=O)=NC=1.C([Zn]C#N)#N>CN(C=O)C.[OH-].[Na+].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.C(Cl)CCl>[C:40]([C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][C@@H:12]2[CH2:15][C@H:14]([C:16]3[N:20]4[C:21]5[CH:27]=[CH:26][N:25]([S:28]([C:31]6[CH:37]=[CH:36][C:34]([CH3:35])=[CH:33][CH:32]=6)(=[O:30])=[O:29])[C:22]=5[N:23]=[CH:24][C:19]4=[N:18][N:17]=3)[C:13]2([CH3:39])[CH3:38])(=[O:9])=[O:10])=[N:6][CH:7]=1)#[N:43]

참가 물질

10

반응물 5

HCID 81531DiisopropylethylamineHCID 11183048(1S,3R)-3-acetamido-2,2-dimethylcyclobutane-1-carboxylic acidHCID 445580975-Bromopyridine-2-sulfonyl chlorideHCID 580103065-bromo-N-((1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutyl)pyridine-2-sulfonamideHCID 178514179HCID 178514179, 화합물

생성물 1

HCID 580102855-cyano-N-((1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutyl)pyridine-2-sulfonamide수율 14%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 111,2-Dichloroethane용매HCID 6228Dimethylformamide용매HCID 14798Sodium Hydroxide용매

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온도
80 °C

실험 절차

To a solution of 5-bromo-N-((1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutyl)pyridine-2-sulfonamide (0.69 g, 1.1 mmol, prepared using A from (1S,3R)-3-acetamido-2,2-dimethylcyclobutanecarboxylic acid [Tetrahedron: Asymmetry 2008, 19, 302-308] and Preparation #9 with EDC, C with DIEA, JJ, N from 5-bromopyridine-2-sulfonyl chloride [Chem Impex]) in degassed DMF (1.5 mL) was added dicyanozinc (0.321 g, 2.74 mmol) followed by Pd(Ph3P)4 (0.063 g, 0.055 mmol, Strem). The reaction was heated at about 80° C. for about 16 h under a nitrogen atmosphere. The reaction mixture was allowed to cool to ambient temperature before it was diluted with aqueous NaOH (1N, 10 mL) and extracted with EtOAc (25 mL). The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The product was purified by silica gel chromatography (12 g) eluting with a gradient of 1-10% MeOH in DCM to give 5-cyano-N-((1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutyl)pyridine-2-sulfonamide (0.09 g, 14%) as a tan solid: LC/MS (Table 2, Method a) Rt=2.14 min; MS m/z: 577 (M+H)+.

후처리

  1. temperatureto cool to ambient temperature before it
  2. extractionextracted with EtOAc (25 mL)
  3. washThe organic layer was washed with brine (20 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe product was purified by silica gel chromatography (12 g)
  8. washeluting with a gradient of 1-10% MeOH in DCM

출처 및 근거

ORD 기록
ord-8ebdba67acc84d92aea54b87a60342eb
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962629B2

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