Lithium Chloride → 2-(benzylamino)-5-(4-(benzyloxy)-3-fluorophenyl)-3-methylpyrimidin-4(3H)-one

HRID 1676383노트

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HRID 1676383 반응식
[CH2:1]([NH:8][C:9]1[N:14]([CH3:15])[C:13](=[O:16])[C:12](Br)=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][C:27]=1[F:35])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([NH:8][C:9]1[N:14]([CH3:15])[C:13](=[O:16])[C:12]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[C:27]([F:35])[CH:28]=2)=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 3

HCID 433294Lithium ChlorideHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 673473372-(benzylamino)-5-bromo-3-methylpyrimidin-4(3H)-one

생성물 1

HCID 673481582-(benzylamino)-5-(4-(benzyloxy)-3-fluorophenyl)-3-methylpyrimidin-4(3H)-one

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 10340Sodium Carbonate용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

A suspension of 2-(benzylamino)-5-bromo-3-methylpyrimidin-4(3H)-one (0.130 g, 0.442 mmol), 4-(benzyloxy)-3-fluorophenylboronic acid (0.130 g, 0.530 mmol), Pd(PPh3)4 (0.026 g, 0.022 mmol) and lithium chloride (0.075 g, 1.77 mmol) in dioxane (2 mL) and 2M aqueous Na2CO3 (2 mL) was stirred at 100° C. for 1 hour. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 10:1 CH2Cl2/EtOAc. The product was obtained (146 mg; 80%) as an off-white foam solid. 1H NMR (400 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.55 (dd, 1H), 7.48-7.43 (m, 2H), 7.43-7.29 (m, 8H), 7.26-7.15 (m, 2H), 5.18 (s, 2H), 4.62 (d, 2H), 3.42 (s, 3H). LRMS (APCI pos) m/e 416 (M+1).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe layers were separated
  4. extractionthe aqueous layer was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography
  9. washeluting with 10:1 CH2Cl2/EtOAc
  10. customThe product was obtained (146 mg; 80%) as an off-white foam solid

출처 및 근거

ORD 기록
ord-90206c25f7444b0fbf3d02c6fb2aeef5
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003662B2

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