Sodium Carbonate → (S)-3-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)-2-hydroxypropanoic acid

HRID 1752415ノート

反応式

HRID 1752415 の反応式
[C:1]([C:4]1[N:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][CH2:12][C@H:13]([OH:18])[C:14]([O:16]C)=[O:15])[CH:5]=1)(=[O:3])[NH2:2].[F:19][C:20]1[CH:41]=[CH:40][C:23]([O:24][C:25]2[CH:30]=[CH:29][C:28](B3OC(C)(C)C(C)(C)O3)=[CH:27][CH:26]=2)=[CH:22][CH:21]=1.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]>[C:1]([C:4]1[N:9]=[C:8]([C:28]2[CH:27]=[CH:26][C:25]([O:24][C:23]3[CH:22]=[CH:21][C:20]([F:19])=[CH:41][CH:40]=3)=[CH:30][CH:29]=2)[N:7]=[C:6]([NH:11][CH2:12][C@H:13]([OH:18])[C:14]([OH:16])=[O:15])[CH:5]=1)(=[O:3])[NH2:2]

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 666684382-[4-(4-Fluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 89422638(S)-methyl 3-((6-carbamoyl-2-chloropyrimidin-4-yl)amino)-2-hydroxypropanoate

生成物 1

HCID 71283948(S)-3-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)-2-hydroxypropanoic acid収率 9%

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 mixture of the (S)-methyl 3-((6-carbamoyl-2-chloropyrimidin-4-yl)amino)-2-hydroxypropanoate (0.408 g, 1.49 mmol) in dioxane (10 mL) was added 2-(4-(4-fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.517 g, 1.65 mmol), 2M aqueous Na2CO3 (1.50 mL, 3.00 mmol) and PdCl2(dppf) (0.066 g, 0.081 mmol). The reaction vessel was flushed with argon, sealed and heated at 100° C. overnight. After cooling, the reaction mixture was diluted with acetone and decanted. Water was added to the insoluble residue to make a suspension. The solid was filtered, washed successively with water, acetone, 1N aqueous HCl then MeOH. The solid was dried under vacuum at 40° C. to give the product (S)-3-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)amino)-2-hydroxypropanoic acid as a light tan powder (0.053 g, 0.13 mmol, 9% yield). 1H NMR (400 MHz, DMSO-d6): 12.61 (1H, s), 8.53 (2H, d, J=8.3 Hz), 8.27 (1H, s), 7.99-7.93 (1H, s), 7.73 (1H, s), 7.31-7.24 (2H, m), 7.19-7.13 (2H, m), 7.08-7.01 (3H, m), 5.60 (1H, s), 4.26 (1H, s), 3.90-3.80 (1H, s), 3.64-3.54 (1H, m). LC/MS: m/z=413.1 [M+H]+.

後処理

  1. customThe reaction vessel was flushed with argon
  2. customsealed
  3. temperatureAfter cooling
  4. additionthe reaction mixture was diluted with acetone
  5. customdecanted
  6. additionWater was added to the insoluble residue
  7. filtrationThe solid was filtered
  8. washwashed successively with water, acetone, 1N aqueous HCl
  9. customThe solid was dried under vacuum at 40° C.

出典と根拠

ORDレコード
ord-936cbf557c7245b6a31b3aa1d36b2fd4
出典データセット
uspto-grants-2015_10
特許番号
US09163008B2

反応ノート

読み込み中…