Acetic Acid → 5-(2,4-dimethyl-1,3-oxazol-5-yl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione hydrochloride

HRID 12791ノート

反応式

HRID 12791 の反応式
[CH3:1][C:2]1[O:3][C:4]([C:8]2[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH:16]=O)[CH:13]=2)=[C:5]([CH3:7])[N:6]=1.[F:20][C:21]([F:35])([F:34])[C:22]1[CH:27]=[CH:26][C:25]([C@:28]23[CH2:33][C@H:32]2[CH2:31][NH:30][CH2:29]3)=[CH:24][CH:23]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+].[Cl:56]C(Cl)C>>[ClH:56].[CH3:1][C:2]1[O:3][C:4]([C:8]2[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH2:16][N:30]3[CH2:31][C@H:32]4[C@:28]([C:25]5[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:35])[F:34])=[CH:27][CH:26]=5)([CH2:33]4)[CH2:29]3)[CH:13]=2)=[C:5]([CH3:7])[N:6]=1

参加物

7

反応物 6

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 589942333-[5-(2,4-Dimethyl-oxazol-5-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehydeHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

生成物 1

HCID 675196555-(2,4-dimethyl-1,3-oxazol-5-yl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione hydrochloride

反応条件

温度
0 °C

実験手順

To a solution of 3-[5-(2,4-Dimethyl-oxazol-5-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep64, 74 mg, 0.28 mmol) in dichloroethane (2 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 57.4 mg, 0.25 mmol), AcOH (18.5 mg, 0.28 mmol) and NaBH(AcO)3 (65 mg, 0.31 mmol) were added portionwise at 0° C. The mixture was stirred at 0° C. for further 30 minutes. A 1N solution of NaOH was added and the mixture extracted with EtOAc. The organic phase was treated with PS isocyanate resin, filtered and evaporated under vacuum. The crude was purified by flash chromatography (DCM/MeOH/NH4OH 95:5:05) to give the title compound as free base. The free base was dissolved in dissolved in dioxane and treated with 4N HCl in dioxane (1 eq), to give the title compound as a white powder. (38 mg, 24%)

後処理

  1. extractionthe mixture extracted with EtOAc
  2. additionThe organic phase was treated with PS isocyanate resin
  3. filtrationfiltered
  4. customevaporated under vacuum
  5. customThe crude was purified by flash chromatography (DCM/MeOH/NH4OH 95:5:05)

出典と根拠

ORDレコード
ord-4eeeeddd8290468eac99d3391116e31a
出典データセット
uspto-grants-2010_06
特許番号
US07727988B2

反応ノート

読み込み中…