Acetic Acid → {4-[(S)-1-(4-Fluoro-benzylamino)-3-methyl-butyl]-thiazol-2-yl}-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine

HRID 604896ノート

反応式

HRID 604896 の反応式
Cl.Cl.Cl.[NH2:4][C@H:5]([C:10]1[N:11]=[C:12]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH:26]=[C:25]([CH3:27])[N:24]=[CH:23]3)=[C:18]([O:28][CH3:29])[CH:17]=2)[S:13][CH:14]=1)[CH2:6][CH:7]([CH3:9])[CH3:8].[F:30][C:31]1[CH:38]=[CH:37][C:34]([CH:35]=O)=[CH:33][CH:32]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>O1CCCC1>[F:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH:4][C@H:5]([C:10]2[N:11]=[C:12]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH:26]=[C:25]([CH3:27])[N:24]=[CH:23]4)=[C:18]([O:28][CH3:29])[CH:17]=3)[S:13][CH:14]=2)[CH2:6][CH:7]([CH3:8])[CH3:9])=[CH:33][CH:32]=1

参加物

7

反応物 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 680234-FluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 86624689[4-((S)-1-amino-3-methyl-butyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine trihydrochloride

生成物 1

HCID 86624691{4-[(S)-1-(4-Fluoro-benzylamino)-3-methyl-butyl]-thiazol-2-yl}-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

96 mg (0.2 mmol) [4-((S)-1-Amino-3-methyl-butyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine trihydrochloride was suspended in tetrahydrofurane (3 ml). At room temperature under nitrogen 103 mg (0.8 mmol) N,N-diisopropyl ethyl amine was added and the reaction was stirred for 10 minutes. 28 mg (0.22 mmol) 4-fluorobenzaldehyde, 24 mg (0.4 mmol) acetic acid and 127 mg (0.6 mmol) sodium triacetoxyborohydride were added and the reaction was stirred at room temperature over night. 2N aqueous NaOH solution (6 ml) was added and the reaction was extracted twice with diethyl ether. The combined organic layers were washed with brine, dried over sodium sulphate, filtered and the solvent was evaporated under reduced pressure. The crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 48 mg (50%) of {4-[(S)-1-(4-fluoro-benzylamino)-3-methyl-butyl]-thiazol-2-yl}-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a yellow solid. MS ISP (m/e): 480.1 (100) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.37 (s, 1H), 7.89 (s, 1H), 7.65 (s, 1H), 7.34-7.31 (m, 3H), 7.24 (d, 1H), 7.13-7.02 (m, 4H), 6.67 (s, 1H), 3.77 (m, 4H), 3.69 (d, 1H), 3.53-3.49 (m, 3H), 2.14 (s, 3H), 1.59-1.51 (m, 3H), 0.85 (d, 3H), 0.78 (d, 3H).

後処理

  1. additionAt room temperature under nitrogen 103 mg (0.8 mmol) N,N-diisopropyl ethyl amine was added
  2. stirringthe reaction was stirred at room temperature over night
  3. extractionthe reaction was extracted twice with diethyl ether
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customthe solvent was evaporated under reduced pressure
  8. customThe crude product was purified on silica gel with methylene chloride/methanol 19/1 yielding 48 mg (50%) of {4-[(S)-1-(4-fluoro-benzylamino)-3-methyl-butyl]-thiazol-2-yl}-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a yellow solid

出典と根拠

ORDレコード
ord-b8ad9a72aa7a41579552c9695cee63bc
出典データセット
uspto-grants-2011_03
特許番号
US07910740B2

反応ノート

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