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

HRID 1192286Notes

Reaction equation

HRID 1192286 reaction equation
[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]

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(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.

Workup

  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

Sources & evidence

ORD record
ord-d15871a50726428c8651fb41c50fc2c6
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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