Diisopropylethylamine → Methyl ((S)-3-methyl-1-oxo-1-((S)-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-yl)carbamate

HRID 71673ノート

反応式

HRID 71673 の反応式
C(N(C(C)C)CC)(C)C.Cl.[NH:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([B:27]3[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]3)=[CH:23][CH:22]=2)=[CH:19][N:20]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[CH3:60][O:61][C:62]([NH:64][C@@H:65]([CH:69]([CH3:71])[CH3:70])[C:66](O)=[O:67])=[O:63]>CN(C)C=O.C(OCC)(=O)C>[CH3:60][O:61][C:62](=[O:63])[NH:64][C@H:65]([C:66]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:26]=[CH:25][C:24]([B:27]3[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]3)=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:67])[CH:69]([CH3:71])[CH3:70]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 66620496(S)-2-(pyrrolidin-2-yl)-5-(4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl)-1H-imidazole hydrochloride

生成物 1

HCID 57462153Methyl ((S)-3-methyl-1-oxo-1-((S)-2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-yl)carbamate収率 68.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Diisopropylethylamine (7.63 mL, 43.8 mmol) was added to a suspension of (S)-2-pyrrolidin-2-yl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazole hydrochloride (7.33 g, 19.5 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (7.6 g, 19.9 mmol) and (S)-2-methoxycarbonylamino-3-methyl-butyric acid (3.59 g, 20.5 mmol) in dimethylformamide (75 mL). All solids dissolved. After 30 min the reaction mixture was diluted with ethyl acetate (300 mL) and was washed with ½ saturated sodium chloride (1×300 mL), half saturated sodium bicarbonate (2×150 mL) and brine (1×100 mL). The organic phase was dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The resulting tan foam was subjected to silica gel chromatography with eluate of 20-100% ethyl acetate and hexanes, to provide (S,S)-[2-methyl-1-(2-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (6.6 g, 68%) as a white foam: 1H (DMSO-d6): δ=11.81 (br s, 1H), 7.72 (m, 2H), 7.61 (m, 2H), 7.51 (br s, 1H), 7.27 (d, J=8.4 Hz, 1H), 5.05 (m, 1H), 4.04 (m, 2H), 3.78 (m, 2H), 3.52 (s, 3H), 2.11 (m, 2H), 1.93 (m, 2H), 1.28 (s, 12H), 0.85 (dd, J1=6.6 Hz, J2=11.4 Hz, 6H).

後処理

  1. dissolutionAll solids dissolved
  2. washwas washed with ½ saturated sodium chloride (1×300 mL), half saturated sodium bicarbonate (2×150 mL) and brine (1×100 mL)
  3. dry with materialThe organic phase was dried with sodium sulfate
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-814125c417d244bca6798246917c738c
出典データセット
uspto-grants-2014_09
特許番号
US08822430B2

反応ノート

読み込み中…