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

HRID 2241240ノート

反応式

HRID 2241240 の反応式
Br[C:2]1[C:3](=[O:14])[N:4]([CH3:13])[C:5]([NH:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[N:6][CH:7]=1.[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][C:24]=1[F:32])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=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>[CH2:15]([O:22][C:23]1[CH:28]=[CH:27][C:26]([C:2]2[C:3](=[O:14])[N:4]([CH3:13])[C:5]([NH:8][CH2:9][CH:10]3[CH2:12][CH2:11]3)=[N:6][CH:7]=2)=[CH:25][C:24]=1[F:32])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

参加物

7

反応物 3

HCID 433294Lithium ChlorideHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 685168835-bromo-2-(cyclopropylmethylamino)-3-methylpyrimidin-4(3H)-one

生成物 1

HCID 685137375-(4-(benzyloxy)-3-fluorophenyl)-2-(cyclopropylmethylamino)-3-methylpyrimidin-4(3H)-one収率 78%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 10340Sodium Carbonate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A suspension of 5-bromo-2-(cyclopropylmethylamino)-3-methylpyrimidin-4(3H)-one (0.112 g, 0.434 mmol), 4-(benzyloxy)-3-fluorophenylboronic acid (0.128 g, 0.521 mmol), Pd(PPh3)4 (0.025 g, 0.022 mmol) and lithium chloride (0.092 g, 2.17 mmol) in dioxane (1.5 mL) and 2M aqueous Na2CO3 (1.5 mL) was stirred at 100° C. for 30 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The phases were separated, and the aqueous phase was re-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude black solid. The crude product was purified by flash column chromatography, eluting with 10:1 dichloromethane/EtOAc. The desired product (0.128 g, 78%) was obtained as a foamy off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.93 (s, 1H), 7.57 (dd, J=2.0, 13.7 Hz, 1H), 7.49-7.31 (m, 7H), 7.19 (t, J=9.0 Hz, 1H), 5.19 (s, 2H), 3.35 (s, 3H), 3.24 (t, J=6.1 Hz, 2H), 1.16 (m, 1H), 0.44 (m, 2H), 0.25 (m, 1H). LRMS (APCI pos) m/e 380 (M+1).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude black solid
  9. customThe crude product was purified by flash column chromatography
  10. washeluting with 10:1 dichloromethane/EtOAc

出典と根拠

ORDレコード
ord-17d152d1578b4de5bc01f8521ef2b3a0
出典データセット
uspto-grants-2010_05
特許番号
US07723330B2

反応ノート

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