Trifluoroacetic acid → tert-butyl ((6-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)methyl)carbamate

HRID 1487536ノート

反応式

HRID 1487536 の反応式
Br[C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[S:8][C:5]2=[N:6][CH:7]=1.[Cl:20][CH:21]([Cl:40])[C:22]([NH:24][C@H:25]([CH2:38][F:39])[C@H:26]([OH:37])[C:27]1[CH:32]=[CH:31][C:30]([Sn](C)(C)C)=[CH:29][CH:28]=1)=[O:23].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(NC(=O)[O-])(C)(C)C.FC(F)(F)C(O)=O>CN(C)C=O.O.C(Cl)Cl.C1(C)C=CC=CC=1>[Cl:20][CH:21]([Cl:40])[C:22]([NH:24][C@H:25]([CH2:38][F:39])[C@@H:26]([C:27]1[CH:28]=[CH:29][C:30]([C:2]2[CH:3]=[C:4]3[N:10]=[C:9]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[S:8][C:5]3=[N:6][CH:7]=2)=[CH:31][CH:32]=1)[OH:37])=[O:23]

参加物

10

反応物 5

HCID 6422Trifluoroacetic acidHCID 521585Tris(furan-2-yl)phosphaneHCID 21252905Tert-butylcarbamateHCID 866953832,2-Dichloro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-trimethylstannanyl-phenyl)-ethyl]-acetamideHCID 86695489Tert-butyl ((6-bromothiazolo[5,4-b]pyridin-2-yl)methyl)carbamate

生成物 1

HCID 86695488tert-butyl ((6-(4-((1R,2S)-2-(2,2-dichloroacetamido)-3-fluoro-1-hydroxypropyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)methyl)carbamate収率 16.4%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
65 °C

実験手順

A mixture of tert-butyl ((6-bromothiazolo[5,4-b]pyridin-2-yl)methyl)carbamate (156 mg, 0.45 mmol), 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(trimethylstannyl)phenyl)-propan-2-yl)acetamide (200 mg, 0.45 mmol) and tris(2-furyl)phosphine (21 mg, 0.090 mmol) Tris(dibenzylideneacetone) dipalladium(0) (41 mg, 0.045 mmol) in dimethylformamide (2.5 mL) is heated at 65° C. for 3 hours under nitrogen. The mixture is then cooled, diluted with water (10 mL) and extracted with ethyl acetate (3×10 mL). Extracts are dried over Na2SO4 and concentrated to get crude title compound. m/z (CI) M+1 543. To a solution of crude tert-butylcarbamate (200 mg, 0.452 mmol) in DCM (3 mL) is added trifluoroacetic acid (0.5 mL) and stirred at room temperature for 3 hours. Reaction is diluted with toluene (10 mL), concentrated under vacuum, basified with saturated aq NaHCO3 and extracted using ethyl acetate (3×10 mL). Extracts are dried over Na2SO4, concentrated and crude compound adsorbed on celite and purified on silica gel column using 0 to 20% methanol in ethyl acetate to give the title compound (40 mg). 1HNMR (DMSO-d6): 4.17 (m, 2H). 4.27 (m, 1.5H), 4.43 (m, 0.5H), 4.59 (m, 0.5H), 4.70 (m, 0.5H), 4.93 (m, 1H), 6.01 (m, 1H), 6.54 (1H), 7.50 (d, 2H), 7.80 (d, 2H), 8.51 (m, 1H), 8.64 (d, 1H), 8.87 (d, 1H), m/z (CI) M+H 443.

後処理

  1. temperatureThe mixture is then cooled
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. dry with materialExtracts are dried over Na2SO4
  4. concentrationconcentrated
  5. customto get crude title compound
  6. customReaction
  7. concentrationconcentrated under vacuum
  8. extractionextracted
  9. dry with materialExtracts are dried over Na2SO4
  10. concentrationconcentrated
  11. custompurified on silica gel column

出典と根拠

ORDレコード
ord-0ab753620d244551a768637f1e7c1a4f
出典データセット
uspto-grants-2016_08
特許番号
US09428528B2

反応ノート

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