HOAt → [(2R,5S)-5-(6-Amino-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

HRID 538360

反応式

HRID 538360 の反応式
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1[C@:9]([CH3:27])([C:23]([F:26])([F:25])[F:24])[O:10][CH2:11][C@:12]([C:15]2[C:20]([F:21])=[CH:19][CH:18]=[C:17]([NH2:22])[N:16]=2)([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].ClC1C(C(O)=O)=NC=C(C#N)C=1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1[C@:9]([CH3:27])([C:23]([F:26])([F:24])[F:25])[O:10][CH2:11][C@@:12]([C:15]2[C:20]([F:21])=[CH:19][CH:18]=[C:17]([NH2:22])[N:16]=2)([CH3:14])[N:13]=1)([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 4

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 508531763-Chloro-5-cyanopyridine-2-carboxylic acidHCID 68108306[(2R,5R)-5-(6-amino-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

生成物 1

HCID 68108222[(2R,5S)-5-(6-Amino-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester収率 76%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of [(2R,5R)-5-(6-amino-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (406 mg, 0.999 mmol), 3-chloro-5-cyanopicolinic acid (201 mg, 1.099 mmol), HOAt (245 mg, 1.798 mmol) and EDC hydrochloride (287 mg, 1.499 mmol) was stirred in DMF (10.2 ml) at rt for 44 hours. The reaction mixture was diluted with toluene and washed with sat. aq. sodium bicarbonate solution, water and brine, dried over sodium sulfate, filtered and evaporated. The crude product (595 mg) was chromatographed over silicagel (toluene: ethyl acetate 9:1) to yield the title compound: 455 mg (76% yield).

後処理

  1. washwashed with sat. aq. sodium bicarbonate solution, water and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product (595 mg) was chromatographed over silicagel (toluene: ethyl acetate 9:1)

出典と根拠

ORDレコード
ord-d275b31a02f6480897683c7bb011d523
出典データセット
uspto-grants-2014_10
特許番号
US08865712B2

関連ノート

読み込み中…