Sodium Carbonate → HCID 71283445、化合物

HRID 1752404ノート

反応式

HRID 1752404 の反応式
[NH2:1][C:2](=[O:16])[C@@H:3]([NH:5][C:6]1[N:11]=[C:10](Cl)[N:9]=[C:8]([C:13]([NH2:15])=[O:14])[CH:7]=1)[CH3:4].CC1(C)C(C)(C)OB([C:25]2[CH:30]=[CH:29][C:28]([O:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=3)=[CH:27][CH:26]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2](=[O:16])[C@@H:3]([NH:5][C:6]1[N:11]=[C:10]([C:25]2[CH:26]=[CH:27][C:28]([O:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]([F:39])([F:40])[F:41])=[CH:34][CH:33]=3)=[CH:29][CH:30]=2)[N:9]=[C:8]([C:13]([NH2:15])=[O:14])[CH:7]=1)[CH3:4]

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 66806437HCID 66806437、化合物HCID 89422280HCID 89422280、化合物

生成物 1

HCID 71283445HCID 71283445、化合物収率 64%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a suspension of (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-chloropyrimidine-4-carboxamide (0.244 g, 1.00 mmol) in dioxane (5.0 mL) was added 4,4,5,5-tetramethyl-2-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,3,2-dioxaborolane (0.403 g, 1.11 mmol), 2M aqueous Na2CO3 (1.0 mL, 2.0 mmol) and PdCl2(dppf) (0.044 g, 0.054 mmol). The reaction vessel was flushed with argon, sealed, and heated at 100° C. overnight. After cooling, the reaction mixture was evaporated in vacuo and the residue chromatographed over silica gel with 50-100% acetone in hexanes. The product fractions were evaporated in vacuo and the resulting solid triturated with 2 mL MeOH, filtered, and dried under vacuum at 42° C. to give (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(4-(4-(trifluoromethyl)phenoxy)phenyl)pyrimidine-4-carboxamide as a cream-colored powder (0.283 g, 0.635 mmol, 64% yield). 1H NMR (400 MHz, DMSO-d6): 8.61 (2H, d, J=8.8 Hz), 8.31 (1H, s), 7.98 (1H, d, J=6.4 Hz), 7.80-7.73 (3H, m), 7.55 (1H, s), 7.25-7.16 (4H, m), 7.11 (1H, s), 7.01 (1H, s), 4.62-4.53 (1H, m), 1.37 (3H, d, J=7.0 Hz). LC/MS: m/z=446.1 [M+H]+.

後処理

  1. customThe reaction vessel was flushed with argon
  2. customsealed
  3. temperatureAfter cooling
  4. customthe reaction mixture was evaporated in vacuo
  5. customthe residue chromatographed over silica gel with 50-100% acetone in hexanes
  6. customThe product fractions were evaporated in vacuo
  7. customthe resulting solid triturated with 2 mL MeOH
  8. filtrationfiltered
  9. customdried under vacuum at 42° C.

出典と根拠

ORDレコード
ord-82f454708c174ad89540b171e1b2f951
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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