Triethylamine → HCID 52920356, 화합물

HRID 250104

반응식

HRID 250104 반응식
[Cl:1][C:2]1[C:3]([N:9]=[C:10]=S)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.CCN(CC)CC.Cl.Cl.[NH2:21][CH2:22][C@@:23]1([OH:31])[CH:28]2[CH2:29][CH2:30][N:25]([CH2:26][CH2:27]2)[CH2:24]1.C(N=C=NC(C)C)(C)C>CN(C)C=O>[Cl:1][C:2]1[C:3]([NH:9][C:10]2[O:31][C@:23]3([CH2:22][N:21]=2)[CH:28]2[CH2:29][CH2:30][N:25]([CH2:26][CH2:27]2)[CH2:24]3)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 12734DiisopropylcarbodiimideHCID 233404453,5-Dichloro-2-isothiocyanatopyridineHCID 66724709(S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride

생성물 1

HCID 52920356HCID 52920356, 화합물수율 44%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
70 °C

실험 절차

To 3,5-dichloro-2-isothiocyanatopyridine (0.11 g, 0.55 mmol) in N,N-dimethylformamide (10 mL) was added Et3N (0.17 mL, 1.21 mmol) and (S)-3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.13 g, 0.56 mmol) at room temperature. The reaction was stirred at 70° C. for 2 hours. The reaction was cooled to room temperature and concentrated in vacuo. The crude urea was purified by chromatography (Biotage: 85% CHCl3, 14% MeOH, 1% NH4OH). The product was then treated with N,N-dimethylformamide (10 mL) and N,N′-diisopropylcarbodiimide (0.26 mL, 1.65 mmol). The reaction was heated to 70° C. for 2 hours. The reaction was cooled to room temperature and concentrated in vacuo to yield the crude product. The crude product was purified by chromatography (Biotage: 85% CHCl3, 14% MeOH, 1% NH4OH) to yield (R)—N-(3,5-dichloropyridin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.08 g, 0.24 mmol, 44% yield) as a white powder. 1H NMR (500 MHz, DMSO-D6) δ ppm 8.91 (s, 1 H), 8.11-8.17 (m, 1 H), 7.97 (d, J=2.44 Hz, 1 H), 3.84 (d, J=9.77 Hz, 1 H), 3.59 (d, J=9.77 Hz, 1 H), 2.95-3.04 (m, 2 H), 2.72-2.81 (m, 2 H), 2.66 (t, J=7.63 Hz, 2 H), 2.01 (s, 1 H), 1.89 (s, 1 H), 1.54-1.62 (m, 2 H), 1.42-1.50 (m, 1 H). MS (LC/MS) R.T.=0.78; [M+]+=326.1.

후처리

  1. temperatureThe reaction was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe crude urea was purified by chromatography (Biotage: 85% CHCl3, 14% MeOH, 1% NH4OH)
  4. temperatureThe reaction was heated to 70° C. for 2 hours
  5. temperatureThe reaction was cooled to room temperature
  6. concentrationconcentrated in vacuo
  7. customto yield the crude product
  8. customThe crude product was purified by chromatography (Biotage: 85% CHCl3, 14% MeOH, 1% NH4OH)

출처 및 근거

ORD 기록
ord-7b9f86398e9a4a0ab74d117097679cd9
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863291B2

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