Diisopropylethylamine → tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

HRID 516128

反応式

HRID 516128 の反応式
[Cl:1][C:2]1[C:7]2[C:8](=[O:18])[N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:6]=2[C:5]([F:19])=[C:4](Cl)[N:3]=1.[NH2:21][C@@H:22]1[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32].C(N(C(C)C)CC)(C)C>CS(C)=O.CC(O)C>[C:31]([O:30][C:29]([NH:28][C@@H:23]1[C@H:22]([NH:21][C:4]2[N:3]=[C:2]([Cl:1])[C:7]3[C:8](=[O:18])[N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:6]=3[C:5]=2[F:19])[CH2:27][CH2:26][O:25][CH2:24]1)=[O:35])([CH3:34])([CH3:32])[CH3:33]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamateHCID 86654739tert-Butyl 4,6-dichloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

生成物 1

HCID 86654748tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate収率 26.4%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 3776Isopropanol溶媒

反応条件

温度
100 °C

実験手順

A mixture of tert-butyl 4,6-dichloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (1.24 g, 3.85 mmol), tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (1.00 g, 4.62 mmol), diisopropylethylamine (3.36 mL, 19.27 mmol) in DMSO (10 mL) and 2-propanol (40 mL) were heated to 100° C. in an oil bath for 20 h. The reaction was repeated on the same scale and both reaction solutions were combined and concentrated. The mixture was purified via silica gel flash chromatography eluting with EtOAc and hexanes (10-50% EtOAc gradient) to give the title compound as a pale pinkish-white solid (510 mg, 13%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.36 (s, 9 H), 1.50 (s, 3 H), 1.59-1.61 (m, 1 H), 1.97-1.99 (m, 1 H), 1.97-1.99 (m, 1 H), 3.46-3.49 (m, 2 H), 3.80-3.83 (m, 3 H), 4.31-4.33 (m, 1 H), 4.73 (s, 1 H), 6.59 (d, J=7.30 Hz, 1 H), 7.43 (d, J=7.30 Hz, 1 H). [M+H] calc'd for C22H30ClFN4O6, 501; found, 501.

後処理

  1. concentrationconcentrated
  2. customThe mixture was purified via silica gel flash chromatography
  3. washeluting with EtOAc and hexanes (10-50% EtOAc gradient)

出典と根拠

ORDレコード
ord-622700303fa94f2582c1265bc6c9def1
出典データセット
uspto-grants-2015_08
特許番号
US09108970B2

関連ノート

読み込み中…