Diisopropylethylamine → methyl-{3-[4-((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-carbamoyl)-thiazol-2-yl]-prop-2-ynyl}-carbamic acid tert-butyl ester

HRID 470720

反応式

HRID 470720 の反応式
[C:1]([O:5][C:6]([N:8]([CH3:20])[CH2:9][C:10]#[C:11][C:12]1[S:13][CH:14]=[C:15]([C:17]([OH:19])=O)[N:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[CH3:63][NH:64][C@H:65]1[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[CH2:68][CH2:67][CH2:66]1>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([CH3:20])[CH2:9][C:10]#[C:11][C:12]1[S:13][CH:14]=[C:15]([C:17](=[O:19])[N:64]([CH3:63])[C@H:65]2[C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[CH2:68][CH2:67][CH2:66]2)[N:16]=1)([CH3:2])([CH3:3])[CH3:4]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 7128544(R)-N-Methyl-1,2,3,4-tetrahydronaphthalen-1-amineHCID 672524842-[3-(Tert-butoxycarbonyl-methyl-amino)-prop-1-ynyl]-thiazole-4-carboxylic acidHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium

生成物 1

HCID 67252656methyl-{3-[4-((R)-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl-carbamoyl)-thiazol-2-yl]-prop-2-ynyl}-carbamic acid tert-butyl ester収率 61.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 2-[3-(tert-butoxycarbonyl-methyl-amino)-prop-1-ynyl]-thiazole-4-carboxylic acid (1.11 g, 3.75 mmol) in DMF (20 mL) was added diisopropylethylamine (1.93 mL, 11.3 mmol), followed by 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (1.57 g, 4.13 mmol). After stirring 15 min at RT, (1R)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (0.60 g, 3.75 mmol) was added to the reaction mixture. After stirring overnight at RT, solvent was evaporated and the resulting brown oil was dissolved in ethylacetate (30 mL), washed with saturated aqueous sodium bicarbonate solution (50 mL), 1M HCl solution (50 mL), and brine (50 mL). The organic layer was dried over sodium sulfate, filtered, and evaporated under reduced pressure. The crude mixture was purified by column chromatography on silica gel (ethylacetate/cyclohexane 2:8 to 3:7) to give methyl-{3-[4-((R)-methyl-1,2,3,4-tetrahydronaphthalen-1-yl-carbamoyl)-thiazol-2-yl]-prop-2-ynyl}-carbamic acid tert-butyl ester (1.01 g, 61%). 1H-NMR (400 MHz, CDCl3): δ=7.75 (s, 1H (conformers)), 7.03-6.92 (m, 4H), 5.58-5.46 (m, 1H (conformers)), 4.18-4.09 (br, 2H), 2.75 (s, 3H (conformers)), 2.61 (s, 3H), 2.11-1.63 (m, 6H), 1.33 (s, 9H (conformers)). MS: m/z=462 (M+23).

後処理

  1. stirringAfter stirring overnight at RT
  2. customsolvent was evaporated
  3. dissolutionthe resulting brown oil was dissolved in ethylacetate (30 mL)
  4. washwashed with saturated aqueous sodium bicarbonate solution (50 mL), 1M HCl solution (50 mL), and brine (50 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe crude mixture was purified by column chromatography on silica gel (ethylacetate/cyclohexane 2:8 to 3:7)

出典と根拠

ORDレコード
ord-27e4ff0ae52a4ff49b80ae095ed459b5
出典データセット
uspto-grants-2014_01
特許番号
US08629286B2

関連ノート

読み込み中…