Water → 3-(1-(4-(3-(piperidin-1-yl)propoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amine

HRID 1896081노트

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HRID 1896081 반응식
Br[CH:2](C)[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]([C:17]3[C:18]([NH2:33])=[N:19][CH:20]=[C:21]([C:23]4[CH:24]=[N:25][N:26]([CH2:28][CH2:29][CH:30]([CH3:32])[CH3:31])[CH:27]=4)[CH:22]=3)=[N:15][N:14]=[N:13]2)=[C:8]([F:34])[C:7]=1[F:35].[NH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.O.O1CCN(CCCCOC2C=CC(N3C(C4C(N)=NC=C(C5C=NN(CCC(C)C)C=5)C=4)=NN=N3)=C(F)C=2F)CC1>C1COCC1>[N:37]1([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([N:12]3[C:16]([C:17]4[C:18]([NH2:33])=[N:19][CH:20]=[C:21]([C:23]5[CH:24]=[N:25][N:26]([CH2:28][CH2:29][CH:30]([CH3:32])[CH3:31])[CH:27]=5)[CH:22]=4)=[N:15][N:14]=[N:13]3)=[C:8]([F:34])[C:7]=2[F:35])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1

참가 물질

6

반응물 4

HCID 962WaterHCID 8082PiperidineHCID 67377779HCID 67377779, 화합물HCID 673779643-(1-(4-(3-bromobutoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amine2회

생성물 1

HCID 673779123-(1-(4-(3-(piperidin-1-yl)propoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amine수율 78%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

As shown in step 5-iii of Scheme 5,3-(1-(4-(3-bromobutoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amine (Compound 1021, 111 mg, 0.203 mmol) was dissolved in 5 mL of THF and cooled to 0° C. The mixture was treated with piperidine (0.06 mL, 0.61 mmol), warmed to 70° C., and stirred for 16 hours. The reaction was cooled to room temperature, treated with cold water, and extracted with CHCl3 (50 mL). The organics were washed with water, washed with brine, dried over sodium sulfate, filtered, and the volatiles removed under reduced pressure. The residue was purified by silica gel chromatography (5% MeOH/CHCl3) to provide 3-(1-(4-(3-(piperidin-1-yl)propoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amine (Compound 150, 70 mg, 78% yield).

후처리

  1. temperaturewarmed to 70° C.
  2. temperatureThe reaction was cooled to room temperature
  3. extractionextracted with CHCl3 (50 mL)
  4. washThe organics were washed with water
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe volatiles removed under reduced pressure
  9. customThe residue was purified by silica gel chromatography (5% MeOH/CHCl3)

출처 및 근거

ORD 기록
ord-9800c1489d6a43ddafbff17df1b4a27d
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518938B2

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