Sodium borohydride → (2R)-2-[(2-Aminoethyl)amino]-3-(4-chlorophenyl)-1-(4-quinazolin-4-yl-piperazin-1-yl)-propan-1-one

HRID 1192286노트

반응식

HRID 1192286 반응식
[NH2:1][C@H:2]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH2:7][CH2:6]1)=[O:4].[C:29]([CH:36]([NH2:39])C=O)(OC(C)(C)C)=O.[BH4-].[Na+]>CO>[NH2:39][CH2:36][CH2:29][NH:1][C@H:2]([CH2:21][C:22]1[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=[CH:13][N:12]=2)[CH2:7][CH2:6]1)=[O:4]

참가 물질

5

반응물 3

HCID 4311764Sodium borohydrideHCID 11246455(R)-2-amino-3-(4-chlorophenyl)-1-(4-(quinazolin-4-yl)piperazin-1-yl)propan-1-oneHCID 57245992BOC-amino-acetaldehyde

생성물 1

HCID 59395971(2R)-2-[(2-Aminoethyl)amino]-3-(4-chlorophenyl)-1-(4-quinazolin-4-yl-piperazin-1-yl)-propan-1-one수율 63.5%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

(2R)-2-Amino-3-(4-chlorophenyl)-1-(4-quinazolin-4-yl-piperazin-1-yl)-propan-1-one (free-base, 41 mg, 0.104 mmol) was stirred at room temperature with Boc-2-aminoacetaldehyde (16 mg, 0.104 mmol) in 0.7 mL methanol for 1 hour, after which NaBH4 (6 mg, 0.160 mmol) was added. The reaction mixture was stirred for 3 hours and then quenched with 1N NaOH. The reaction mixture was extracted with DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation. The crude residue was purified on silica (15:1 DCM/MeOH). The resulting Boc-amine intermediate was treated with 1.4 mL 4M HCl/dioxane and stirred at room temperature for 14 hours, after which the reaction mixture was diluted with ether. The solids were isolated by filtration with nitrogen pressure and dried under reduced pressure to give the desired product (29 mg, 51%) as the trihydrochloride salt. Rt 1.69. MS (CI+) [M+H]+ 439.

후처리

  1. customquenched with 1N NaOH
  2. extractionThe reaction mixture was extracted with DCM
  3. dry with materialthe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customThe crude residue was purified on silica (15:1 DCM/MeOH)
  7. additionThe resulting Boc-amine intermediate was treated with 1.4 mL 4M HCl/dioxane
  8. stirringstirred at room temperature for 14 hours
  9. additionafter which the reaction mixture was diluted with ether
  10. customThe solids were isolated by filtration with nitrogen pressure
  11. customdried under reduced pressure

출처 및 근거

ORD 기록
ord-d15871a50726428c8651fb41c50fc2c6
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680114B2

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