Sodium Carbonate → (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)pyrimidine-4-carboxamide

HRID 1752447ノート

反応式

HRID 1752447 の反応式
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[CH:16]=[CH:15][C:14](B4OC(C)(C)C(C)(C)O4)=[CH:13][CH:12]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.[NH2:26][C:27](=[O:41])[C@@H:28]([NH:30][C:31]1[N:36]=[C:35](Cl)[N:34]=[C:33]([C:38]([NH2:40])=[O:39])[CH:32]=1)[CH3:29].C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[NH2:26][C:27](=[O:41])[CH:28]([NH:30][C:31]1[N:36]=[C:35]([C:14]2[CH:13]=[CH:12][C:11]([O:10][C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)=[CH:16][CH:15]=2)[N:34]=[C:33]([C:38]([NH2:40])=[O:39])[CH:32]=1)[CH3:29].[NH2:26][C:27](=[O:41])[C@@H:28]([NH:30][C:31]1[N:36]=[C:35]([C:14]2[CH:13]=[CH:12][C:11]([O:10][C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)=[CH:16][CH:15]=2)[N:34]=[C:33]([C:38]([NH2:40])=[O:39])[CH:32]=1)[CH3:29]

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 712856355-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]-1,3-benzodioxoleHCID 89422280HCID 89422280、化合物

生成物 2

HCID 71283206(S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)pyrimidine-4-carboxamide収率 87.2%HCID 71283211HCID 71283211、化合物

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A 50-mL vial with a screw-top septum was charged with 200 mg of 2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, 1 equivalent of (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-chloropyrimidine-4-carboxamide (1.53 mg, 0.59 mmol), 1.5 mL 2M aqueous Na2CO3, 0.07 equivalents of PdCl2(PPh3)2 (28 mg, 0.04 mmol), and 8 mL dioxane. The vial was purged with nitrogen and heated to 100° C. for 6 h, at which time the reaction was complete. The mixture was diluted with 100 mL EtOAc and washed two times with 100 mL water. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was chromatographed by combiflash using a 40-gram silica column with a gradient EtOAc (100% max) in hexane to provide 108 mg (43% yield) of S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(4-(benzo[d][1,3]dioxol-5-yloxy)phenyl)pyrimidine-4-carboxamide as a white solid. m/z 421, 1H NMR (CD3OD): 8.51-8.41 (m, 2H), 7.14-7.07 (s, 1H), 7.01-6.93 (m, 2H), 6.86-6.78 (m, 1H), 6.64-6.60 (m, 1H), 6.57-6.50 (m, 1H), 6.01-5.95 (s, 2H), 4.61-4.49 (m, 1H), 1.56-1.48 (m, 3H).

後処理

  1. customThe vial was purged with nitrogen
  2. additionThe mixture was diluted with 100 mL EtOAc
  3. washwashed two times with 100 mL water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was chromatographed by combiflash

出典と根拠

ORDレコード
ord-d35380ee3fdb4cca9664f83241fb106a
出典データセット
uspto-grants-2015_10
特許番号
US09163008B2

反応ノート

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