2-Fluoro-N-methoxy-N-methylnicotinamide → Tert-butyl 4-(5-(2-fluoronicotinoyl)thiazol-2-yl)-1,4-diazepane-1-carboxylate

HRID 401476노트

반응식

HRID 401476 반응식
C([Li])CCC.[C:6]([O:10][C:11]([N:13]1[CH2:19][CH2:18][CH2:17][N:16]([C:20]2[S:21][CH:22]=[CH:23][N:24]=2)[CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].[F:25][C:26]1[N:37]=[CH:36][CH:35]=[CH:34][C:27]=1[C:28](N(OC)C)=[O:29]>O1CCCC1>[F:25][C:26]1[N:37]=[CH:36][CH:35]=[CH:34][C:27]=1[C:28]([C:22]1[S:21][C:20]([N:16]2[CH2:17][CH2:18][CH2:19][N:13]([C:11]([O:10][C:6]([CH3:9])([CH3:7])[CH3:8])=[O:12])[CH2:14][CH2:15]2)=[N:24][CH:23]=1)=[O:29]

참가 물질

5

반응물 3

HCID 534170672-Fluoro-N-methoxy-N-methylnicotinamideHCID 57690677Tert-butyl 4-(thiazol-2-yl)-1,4-diazepane-1-carboxylateHCID 178418339Butyllithium

생성물 1

HCID 57690516Tert-butyl 4-(5-(2-fluoronicotinoyl)thiazol-2-yl)-1,4-diazepane-1-carboxylate수율 38%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
-78 °C

실험 절차

A 2.5M n-butyl lithium in tetrahydrofuran solution (0.9 ml, 2.25 mmol) was added dropwise to a solution of tert-butyl-4-(thiazol-2-yl)-1,4-diazepane-1-carboxylate (570 mg, 2 mmol) in tetrahydrofuran (7 ml), cooled to −78° C. Thirty minutes later, a solution of 2-fluoro-N-methoxy-N-methylnicotinamide (370 mg, 2 mmol) in tetrahydrofuran (2 ml) added dropwise. The reaction mixture was stirred at −78° C. for one hour, then at 0° C. for an extra hour. It was quenched with a saturated sodium bicarbonate aqueous solution. The reaction mixture was diluted with ethyl acetate, then washed with brine. The organic was dried over magnesium sulfate, then concentrated in vacuo. The residue was purified by flash chromatography (40 g silica gel, pentane/ethyl acetate) to afford the title compound (300 mg, 38%). 1H NMR (CD3OD): 1.42 (9H, s), 1.90-2.00 (2H, MO, 3.45-3.50 (2H, m)<3.65-6.75 (2H, m), 3.80-3.90 (2H, m), 7.46-7.49 (1H, t), 7.67-7.69 (1H, d), 8.10-8.15 (1H, t), 8.39-8.40 (1H, d). MS (ES+): 407.

후처리

  1. waitat 0° C. for an extra hour
  2. customIt was quenched with a saturated sodium bicarbonate aqueous solution
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic was dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (40 g silica gel, pentane/ethyl acetate)

출처 및 근거

ORD 기록
ord-22ab8ec639b14d0498c4df6ec76ddefb
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08741931B2

반응 노트

불러오는 중…