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 1854329ノート

反応式

HRID 1854329 の反応式
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]

参加物

10

反応物 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、化合物

生成物 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-sulfonamide収率 14%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 111,2-Dichloroethane溶媒HCID 6228Dimethylformamide溶媒HCID 14798Sodium Hydroxide溶媒

反応条件

温度
80 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-8ebdba67acc84d92aea54b87a60342eb
出典データセット
uspto-grants-2015_02
特許番号
US08962629B2

反応ノート

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