Dichloromethane → (R)-N-((S)-1-(2,5-difluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)ethyl)-2-methylpropane-2-sulfinamide

HRID 57428

反応式

HRID 57428 の反応式
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([C@@H:9]([NH:11][S@@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])[CH3:10])=[C:4]([F:18])[CH:3]=1.[CH3:19][N:20]1[CH:24]=[C:23](B(O)O)[CH:22]=[N:21]1.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>[NH4+].[Cl-].CCOC(C)=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].CCOC(C)=O.CCCCCCC.COCCOC>[F:18][C:4]1[CH:3]=[C:2]([C:23]2[CH:22]=[N:21][N:20]([CH3:19])[CH:24]=2)[C:7]([F:8])=[CH:6][C:5]=1[C@@H:9]([NH:11][S@@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])[CH3:10]

参加物

10

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 112635011-Methyl-1H-pyrazole-4-boronic acidHCID 90347558(R)-N-((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

生成物 1

HCID 90416139(R)-N-((S)-1-(2,5-difluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)ethyl)-2-methylpropane-2-sulfinamide収率 73.7%

試薬・触媒・溶媒 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒HCID 25517Ammonium Chloride溶媒HCID 21899848Ethylacetate heptane溶媒

反応条件

温度
100 °C

実験手順

To two microwave vials with stir bars were added (R)—N—((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (500 mg, 1.47 mmol), 1-Methyl-4-1H-pyrazoleboronic acid, pinacol ester (917 mg, 4.41 mmol), DME (6 ml), Na2CO3 (3.67 ml, 7.35 mmol) (2.0 M aq) and PdCl2(dppf).CH2Cl2 adduct (60.0 mg, 0.07 mmol) divided evenly between the two vessels. Vessels were capped and heated by microwave irradiation for 20 min at 100° C. Reaction mixtures were combined, diluted with a saturated solution of NH4Cl and EtOAc. Phases partitioned. Aqueous phase extracted with EtOAc and organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 60 to 100%) provided (R)—N—((S)-1-(2,5-difluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)ethyl)-2-methylpropane-2-sulfinamide (370 mg, 1.08 mmol, 73.7% yield). 1H NMR (400 MHz, CDCL3) δ ppm 1.23 (s, 9H) 1.57-1.60 (m, 3H) 3.33 (d, J=4.06 Hz, 1H) 3.97 (s, 3H) 4.79-4.88 (m, 1H) 7.10 (dd, J=11.20, 6.06 Hz, 1H) 7.20 (dd, J=10.78, 6.19 Hz, 1H) 7.76 (d, J=2.20 Hz, 1H) 7.82 (s, 1H). LCMS m/z 342.1 (M+H)+, Rt 0.77 min.

後処理

  1. customVessels were capped
  2. customReaction mixtures
  3. customPhases partitioned
  4. extractionAqueous phase extracted with EtOAc and organic phases
  5. washwashed with water, brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated onto silica gel

出典と根拠

ORDレコード
ord-5f786cf5a3484828b2217b2c2861b086
出典データセット
uspto-grants-2016_09
特許番号
US09434719B2

関連ノート

読み込み中…