Diisopropylethylamine → 6-((tert-butyldimethylsilyloxy)methyl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide

HRID 572639ノート

反応式

HRID 572639 の反応式
[Si:1]([O:8][CH2:9][C:10]1[N:15]=[C:14]([CH3:16])[N:13]=[C:12]([C:17]([O:19]C)=O)[CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[F:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH2:36])=[CH:33][C:32]=1[O:39][CH3:40]>CO>[Si:1]([O:8][CH2:9][C:10]1[N:15]=[C:14]([CH3:16])[N:13]=[C:12]([C:17]([NH:36][CH2:35][C:34]2[CH:37]=[CH:38][C:31]([F:30])=[C:32]([O:39][CH3:40])[CH:33]=2)=[O:19])[CH:11]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 442031244-Fluoro-3-methoxybenzylamineHCID 70978757Methyl 6-((tert-butyldimethylsilyloxy)methyl)-2-methylpyrimidine-4-carboxylate

生成物 1

HCID 709788136-((tert-butyldimethylsilyloxy)methyl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide収率 81.2%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
70 °C

実験手順

To a stirred solution of methyl 6-((tert-butyldimethylsilyloxy)methyl)-2-methylpyrimidine-4-carboxylate (4.70 g, 15.86 mmol, Preparation #6) in MeOH (50 mL) were added DIEA (8.3 mL, 47.59 mmol Spectrochem) and 4-fluoro-3-methoxybenzylamine (3.8 g, 24.58 mmol, WO 2008/083056). The reaction mixture was heated to about 70° C. for about 15 h. The solvents were removed in vacuo and the crude material partitioned between EtOAc (300 mL) and 1N HCl solution (300 mL). The layers were separated and the aqueous layer extracted with EtOAc (1×150 mL). The combined organic layers were washed successively with 1N HCl solution (1×200 mL), water (1×200 mL) and brine (1×250 mL), dried over sodium sulphate and evaporated to dryness. The residue obtained was purified by silica gel (60-120 mesh) chromatography eluting with 25 to 35% of EtOAc in hexane. Relevant fractions containing the target compound were combined and evaporated to dryness under reduced pressure to afford 6-((tert-butyldimethylsilyloxy)methyl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide 5.4 g (81%); 1H NMR (400 MHz, DMSO): δ 9.431-9.400 (t, J=6.0 Hz, 1H), 7.884 (s, 1H), 7.173-7.112 (m, 2H), 6.897-6.860 (m, 1H), 4.794 (s, 2H), 4.468-4.452 (d, J=6.4 Hz, 2H), 3.814 (s, 3H), 2.68 (s, 3H), 0.934 (s, 9H), 0.118 (s, 6H), MS m/z: 420 (M+H).

後処理

  1. customThe solvents were removed in vacuo
  2. customthe crude material partitioned between EtOAc (300 mL) and 1N HCl solution (300 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with EtOAc (1×150 mL)
  5. washThe combined organic layers were washed successively with 1N HCl solution (1×200 mL), water (1×200 mL) and brine (1×250 mL)
  6. dry with materialdried over sodium sulphate
  7. customevaporated to dryness
  8. customThe residue obtained
  9. customwas purified by silica gel (60-120 mesh) chromatography
  10. washeluting with 25 to 35% of EtOAc in hexane
  11. additionRelevant fractions containing the target compound
  12. customevaporated to dryness under reduced pressure

出典と根拠

ORDレコード
ord-9c08fae67b52493f84877923a16ba1a4
出典データセット
uspto-grants-2015_05
特許番号
US09029409B2

反応ノート

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