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

반응식

HRID 538360 반응식
[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]

참가 물질

7

반응물 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

생성물 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 ester수율 76%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-d275b31a02f6480897683c7bb011d523
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865712B2

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