Diisopropylethylamine → {(1S,3R)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butyl}-carbamic acid t-butyl ester

HRID 19038

反応式

HRID 19038 の反応式
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C@H:14]([O:16][CH2:17][CH3:18])[CH3:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[OH:20][C@@H:21]([CH2:51]O)[CH2:22][N:23]1[CH:27]=[CH:26][C:25]([NH:28]C(=O)[C@@H](N2CC(OC3C=CC=C(Cl)C=3Cl)=CC2=O)CC(C)C)=[N:24]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=C[C:63]=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:10](=[O:12])[NH:28][C:25]1[CH:26]=[CH:27][N:23]([CH2:22][C:21]([OH:20])([CH3:51])[CH3:63])[N:24]=1)[CH2:13][C@H:14]([O:16][CH2:17][CH3:18])[CH3:15])([CH3:2])([CH3:3])[CH3:4]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 66899094HMS5552 HClHCID 86635229HCID 86635229、化合物

生成物 1

HCID 66899703{(1S,3R)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butyl}-carbamic acid t-butyl ester収率 73.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

(2S,4R)-2-t-butoxycarbonylamino-4-ethoxy-pentanoic acid (273 mg, 1.04 mmol) was mixed with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 194.6 mg, 1.25 mmol) in N,N-dimethylformamide (10 mL). benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (695 mg, 1.57 mmol) and N,N-diisopropylethylamine (0.4 mL) was added at 0° C. The mixture was stirred at room temperature overnight. Solvents were evaporated and the residue was extracted with ethyl acetate and saturated sodium chloride solution. Solvents were evaporated and the crude material was purified by flash column chromatography (silica gel, 10-80% ethyl acetate/hexanes) to afford {(1S,3R)-3-ethoxy-1-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylcarbamoyl]-butyl}-carbamic acid t-butyl ester (306 mg, 73%) as a white solid: LR-ES-MS m/z calculated for C19H34N4O5 [M]+ 398, observed [M+H]+ 399; 1H NMR (300 MHz, CDCl3, plus drops of CD3OD) δ ppm 1.08-1.15 (m, 12H), 1.37 (s, 9H), 1.72-1.94 (m, 2H), 3.35-3.60 (m, 3H), 3.89 (s, 2H), 4.20 (m, 1H), 6.48 (br. s., 1H).

後処理

  1. customSolvents were evaporated
  2. extractionthe residue was extracted with ethyl acetate and saturated sodium chloride solution
  3. customSolvents were evaporated
  4. customthe crude material was purified by flash column chromatography (silica gel, 10-80% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-eb49e35cc30b48fe9f55bd625413ca99
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

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