Trifluoroacetic acid → 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrile

HRID 661041ノート

反応式

HRID 661041 の反応式
[C:1]([C:3]1[CH:4]=[C:5]([C:10]2[S:14][C:13]([NH:15][CH2:16][C@@H:17]([NH:29]C(=O)OC(C)(C)C)[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[N:12][CH:11]=2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:29][C@@H:17]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:26])([F:28])[F:27])=[CH:21][CH:20]=1)[CH2:16][NH:15][C:13]1[S:14][C:10]([C:5]2[CH:6]=[CH:7][C:8]([F:9])=[C:3]([CH:4]=2)[C:1]#[N:2])=[CH:11][N:12]=1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acid2 回HCID 86613766tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

生成物 1

HCID 866137675-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrile収率 96%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of tert-butyl (S)-1-(5-(3-cyano-4-fluorophenyl)thiazol-2-ylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.18 g, 0.35 mmol) in 7 mL of DCM was added TFA (0.40 mL, 5.2 mmol). After 30 minutes, 2 mL of additional TFA was added. The mixture was stirred for 30 minutes and was then concentrated under reduced pressure. The residue was taken up in 30 mL of 1:1 EtOAc to 2 N aqueous Na2CO3. The mixture was partitioned in a separatory funnel, and the aqueous portion was extracted with 25 mL of EtOAc. The combined organic extracts were washed with brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (2.5% to 10% MeOH/DCM) afforded 5-(2-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propylamino)thiazol-5-yl)-2-fluorobenzonitrile (0.14 g, 0.33 mmol, 96% yield) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ ppm 7.83 (dd, J=5.8, 2.4 Hz, 1H), 7.76 (ddd, J=8.7, 5.0, 2.4 Hz, 1H), 7.68 (d, J=8.2 Hz, 2H), 7.52 (d, J=7.8 Hz, 2H), 7.48 (s, 1H), 7.35 (t, J=9.0 Hz, 1H), 3.84-3.78 (m, 1H), 3.68-3.63 (m, 1H), 3.55-3.47 (m, 1H), 3.14-3.04 (m, 2H) LCMS (M+H) 421 calc. for C20H19F3N4OS 420.43.

後処理

  1. concentrationwas then concentrated under reduced pressure
  2. customThe mixture was partitioned in a separatory funnel
  3. extractionthe aqueous portion was extracted with 25 mL of EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationFiltration and concentration under reduced pressure

出典と根拠

ORDレコード
ord-d5590b1a032544c8bf685fd13c291b37
出典データセット
uspto-grants-2011_12
特許番号
US08084479B2

反応ノート

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