Methylamine → (3R*,4R*)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158351노트

반응식

HRID 1158351 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH:34]=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:36][NH2:37].[BH4-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([CH2:34][NH:37][CH3:36])[C@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[CH2:12]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

5

반응물 3

HCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 59512275(3S*,4R*)-3-formyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 59512501(3R*,4R*)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

To a solution of (3S,4R)-3-formyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (2.7 g, 5.48 mmol) in MeOH (containing 2% AcOH, 25 mL), methylamine (13.7 mL, 27.41 mmol, 2M in MeOH) is added. The solution is stirred at RT for 1 h under nitrogen atmosphere and cooled to 10° C., before the careful addition of NaBH4 (0.415 g, 10.96 mmol) (exothermic !!). The resulting mixture is allowed to reach RT and stirred for 1.5 h. The excess reducing agent is quenched with water, AcOEt is added and the reaction mixture is poured into an aqueous saturated solution of NaHCO3. The organic layer is separated and the aqueous layer extracted twice with AcOEt, dried over Na2SO4, filtered, and concentrated in vacuo. The crude material is used in the next step without further purification. TLC, Rf (CH2Cl2/MeOH 95:5)=0.05. MS (LC-MS) [M+H]+=508.1. tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 ml/min): 4.53 min.

후처리

  1. customto reach RT
  2. stirringstirred for 1.5 h
  3. customis quenched with water, AcOEt
  4. additionis added
  5. additionthe reaction mixture is poured into an aqueous saturated solution of NaHCO3
  6. customThe organic layer is separated
  7. extractionthe aqueous layer extracted twice with AcOEt
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude material is used in the next step without further purification
  12. customtR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 ml/min)
  13. custom4.53 min.

출처 및 근거

ORD 기록
ord-046d8291435f45998298bdc36a64d3c8
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807709B2

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