Hydrochloric Acid → (S)-1-Isopropyl-4-[1-(2-trifluoromethyl-pyrimidin-5-yl)-piperidine-4-carbonyl]-2-methyl piperazine hydrochloride

HRID 734354

反応式

HRID 734354 の反応式
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[CH:29]([N:32]1[CH2:37][CH2:36][N:35]([C:38]([CH:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)=[O:39])[CH2:34][C@@H:33]1[CH3:46])([CH3:31])[CH3:30].Br[C:48]1[CH:49]=[N:50][C:51]([C:54]([F:57])([F:56])[F:55])=[N:52][CH:53]=1.CC(C)([O-])C.[Na+].[ClH:64]>O1CCOCC1.CO.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[ClH:64].[CH:29]([N:32]1[CH2:37][CH2:36][N:35]([C:38]([CH:40]2[CH2:41][CH2:42][N:43]([C:48]3[CH:49]=[N:50][C:51]([C:54]([F:57])([F:56])[F:55])=[N:52][CH:53]=3)[CH2:44][CH2:45]2)=[O:39])[CH2:34][C@@H:33]1[CH3:46])([CH3:31])[CH3:30]

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 336979635-Bromo-2-(trifluoromethyl)pyrimidineHCID 68815891HCID 68815891、化合物

生成物 1

HCID 68817779(S)-1-Isopropyl-4-[1-(2-trifluoromethyl-pyrimidin-5-yl)-piperidine-4-carbonyl]-2-methyl piperazine hydrochloride

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

Tris(dibenzylideneacetone)dipalladium(0)(30 mg) and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (60 mg) were added to a solution of (S)-1-isopropyl4-(piperidine-4-carbonyl]-2-methyl piperazine (free base compound from D29)(0.134 g) and 5-bromo-2-trifluromethylpyrimidine (D30)(0.12 g) in degassed dioxane (3 ml). This was followed by the addition of sodium-t-butoxide (0.1 g). The reaction was carried out in a Personal Chemistry microwave reactor at 120° C. for 5 min. After cooling the reaction mixture was diluted with methanol (10 ml), the solids were filtered off and the filtrate was applied to an SCX resin column. Initial elution with methanol was followed by elubon with methanolic ammonia (2M). The ammoniacal eluates were concentrated to a gum and further purified by silica gel chromatography, eluting with 0-10% methanolic ammonia (2M) in DCM. Evaporation of the appropriate fractions gave the free base which was dissolved in DCM (3 ml) and treated with ethereal 1M HCl (2 ml) to give the title compound (E89) as a light yellow solid (56 mg). MS electrospray (+ve) 400 (MH+). 1H NMR δ [MeOH-d4]: 1.28-1.29 (3H, m), 1.4-1.5 (8H, m), 1.8-1.9 (4H, m), 2.98-3.2 (3H, m), 3.45-3.57 (3H, m), 4.0-4.08 (3H, m), 4.35-4.45 (1H, m), 4.6-4.78 (1H, s), 8.5 (2H, s).

後処理

  1. temperatureAfter cooling the reaction mixture
  2. filtrationthe solids were filtered off
  3. washInitial elution with methanol
  4. concentrationThe ammoniacal eluates were concentrated to a gum
  5. customfurther purified by silica gel chromatography
  6. washeluting with 0-10% methanolic ammonia (2M) in DCM
  7. customEvaporation of the appropriate fractions
  8. customgave the free base which

出典と根拠

ORDレコード
ord-268f471130dc45d181780c3283eb431e
出典データセット
uspto-grants-2009_09
特許番号
US07592347B2

関連ノート

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