Diisopropylethylamine → Methyl 2-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}-1,2,3,6-Tetrahydropyridin-4-yl)-5-Chlorophenyl]Propanoate

HRID 2415548노트

반응식

HRID 2415548 반응식
C(N(CC)C(C)C)(C)C.Cl.[C:11]([N:15]1[CH2:19][C@@H:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[C@H:17]([C:28](O)=[O:29])[CH2:16]1)([CH3:14])([CH3:13])[CH3:12].[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([C:44]2[CH2:45][CH2:46][NH:47][CH2:48][CH:49]=2)=[C:36]([CH:38]([CH3:43])[C:39]([O:41][CH3:42])=[O:40])[CH:37]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.ON1C2N=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[C:11]([N:15]1[CH2:19][C@@H:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[C@H:17]([C:28]([N:47]2[CH2:46][CH:45]=[C:44]([C:35]3[CH:34]=[CH:33][C:32]([Cl:31])=[CH:37][C:36]=3[CH:38]([CH3:43])[C:39]([O:41][CH3:42])=[O:40])[CH2:49][CH2:48]2)=[O:29])[CH2:16]1)([CH3:12])([CH3:14])[CH3:13]

참가 물질

8

반응물 6

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22640763HCID 22640763, 화합물HCID 67212109(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochloride

생성물 1

HCID 69362634Methyl 2-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}-1,2,3,6-Tetrahydropyridin-4-yl)-5-Chlorophenyl]Propanoate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

N,N-diisopropylethylamine (1.00 mL, 5.76 mmol) was added to a stirred suspension of (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid (1-7) (0.614 g, 1.92 mmol), methyl 2-[5-chloro-2-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]propanoate (2-3) (0.605 g, 1.92 mmol), O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.876 g, 2.30 mmol) and 1-hydroxy-7-azabenzotriazole (0.314 g, 2.30 mmol) in N,N-dimethylformamide (3.8 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted three times with ethyl acetate. The combined organic extracts were washed with water, brine, dried (Na2SO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 0-15% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent) provided 2-4 as a pale yellow oil; (m/z (ES) 545 (MH+).

후처리

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic extracts were washed with water, brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 0-15% methanol (containing 10% v/v ammonium hydroxide)/methylene chloride as eluent)

출처 및 근거

ORD 기록
ord-bbd24837e3544af2ab8fa170ae4ab20f
출처 데이터셋
uspto-grants-2004_11
특허 번호
US06818658B2

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