Morpholine → 2-[3-Methoxy-4-(5-morpholin-4-ylpyridin-2-yl)phenyl]-1,3-benzoxazole

HRID 7791

반응식

HRID 7791 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[O:15][C:16]4[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=4[N:18]=3)=[CH:10][C:9]=2[O:23][CH3:24])=[N:6][CH:7]=1.[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.CC([O-])(C)C.[Na+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:24][O:23][C:9]1[CH:10]=[C:11]([C:14]2[O:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[N:18]=2)[CH:12]=[CH:13][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[CH:7][N:6]=1

참가 물질

6

반응물 4

HCID 8083MorpholineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 103087512-[4-(5-Chloropyridin-2-yl)-3-methoxyphenyl]-1,3-benzoxazoleHCID 23676156Sodium t-butoxide

생성물 1

HCID 102159612-[3-Methoxy-4-(5-morpholin-4-ylpyridin-2-yl)phenyl]-1,3-benzoxazole

시약·촉매·용매 1

HCID 167845palladium(II) acetate촉매

반응 조건

온도
110 °C

실험 절차

2-[4-(5-chloropyridin-2-yl)-3-methoxyphenyl]-1,3-benzoxazole (58 mg, 0.17 mmol), morpholine (18 μL, 0.21 mmol), Pd(OAc)2 (0.38 mg, 0.0017 mmol), 1,1′-biphenyl-2-yl[di(tert-butyl)]phosphine (1.0 mg, 0.0034 mmol), and NaOtBu (23 mg, 0.24 mmol) were combined in a sealable tube evacuated and backfilled with argon. Toluene (800 μL) was added and the mixture was degassed with a stream of argon for 5 min. The tube was sealed and the mixture was heated to 110° C. for 18 h. Crude mixture was adsorbed onto silica gel and purified by automated flash chromatography using an EtOAc/hexanes gradient to afford 2-[3-methoxy-4-(5-morpholin-4-ylpyridin-2-yl)phenyl]-1,3-benzoxazole as a yellow solid. The freebase was dissolved in Et2O/CH2Cl2 and treated with 1N HCl in Et2O. Resulting yellow solid was filtered and dried under high vacuum to afford the desired 2-[3-methoxy-4-(5-morpholin-4-ylpyridin-2-yl)phenyl]-1,3-benzoxazole hydrochloride as a yellow solid: 1H NMR (CD3OD, 300 MHz) δ 8.33–8.30 (d, 1H), 8.20–8.09 (m, 2H), 8.08–8.02 (m, 2H), 7.87–7.77 (m, 2H), 7.75–7.71 (m, 1H), 7.53–7.42 (m, 2H), 4.10 (s, 3H), 3.89 (t, 4H), 3.49–3.47 (t, 4H). MS (ESI) 388 (M+H)+.

후처리

  1. customevacuated
  2. additionToluene (800 μL) was added
  3. customthe mixture was degassed with a stream of argon for 5 min
  4. customThe tube was sealed
  5. custompurified by automated flash chromatography

출처 및 근거

ORD 기록
ord-bfe5da107fae4df59ca40a60daf70ae9
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07087601B2

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