Diisopropylethylamine → (2R,5S)-4-{2-[6-(1,1-Difluoro-propyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475508노트

반응식

HRID 1475508 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][N:15]2[CH2:19][CH2:18][CH2:17][C:16]2=[O:20])[N:11]([CH2:21][C:22](O)=[O:23])[CH2:10][C@H:9]1[CH3:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:26][C:27]([C:31]1[CH:32]=[C:33]2[NH:39][CH2:38][C:37]([CH3:41])([CH3:40])[C:34]2=[N:35][CH:36]=1)([F:30])[CH2:28][CH3:29].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][N:15]2[CH2:19][CH2:18][CH2:17][C:16]2=[O:20])[N:11]([CH2:21][C:22]([N:39]2[C:33]3[C:34](=[N:35][CH:36]=[C:31]([C:27]([F:30])([F:26])[CH2:28][CH3:29])[CH:32]=3)[C:37]([CH3:40])([CH3:41])[CH2:38]2)=[O:23])[CH2:10][C@H:9]1[CH3:25])=[O:7])([CH3:3])([CH3:4])[CH3:2]

참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 709806426-(1,1-Difluoro-propyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridineHCID 70981057(2R,5S)-4-Carboxymethyl-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 70980486(2R,5S)-4-{2-[6-(1,1-Difluoro-propyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester수율 56.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

(2R,5S)-4-Carboxymethyl-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (0.20 g, 0.56 mmol) and 6-(1,1-difluoro-propyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine (0.15 g, 0.6 mmol) were dissolved in DMF (2.8 mL). N,N-Diisopropylethylamine (0.36 g, 2.8 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.43 g, 1.1 mmol) were added and the reaction stirred at room temperature for 18 h. Saturated aqueous sodium bicarbonate (10 mL) was added and the aqueous phase extracted with EtOAc (3×10 mL). The combined organic extracts were diluted with petroleum spirit (20 mL), washed with water (3×), dried with sodium sulfate, filtered and concentrated. Chromatography (silica gel, gradient elution, 0-5%, methanol in EtOAc) gave the title compound (0.178 g), MS: [M+H]+=564.

후처리

  1. extractionthe aqueous phase extracted with EtOAc (3×10 mL)
  2. additionThe combined organic extracts were diluted with petroleum spirit (20 mL)
  3. washwashed with water (3×)
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washChromatography (silica gel, gradient elution, 0-5%, methanol in EtOAc)

출처 및 근거

ORD 기록
ord-a20e8f9ef24a4de792e81d5d2aba744b
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018214B2

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