Sodium triacetoxyborohydride → tert-Butyl 7-{2-[1-(2-amino-pyrimidin-4-yl)-ethylamino]-benzoylamino}-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylate

HRID 969700Notes

Reaction equation

HRID 969700 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8](=O)[CH3:9])[CH:5]=[CH:4][N:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:27][C:26]([CH3:29])([CH3:28])[C:25]2[C:20](=[CH:21][C:22]([NH:30][C:31](=[O:39])[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[NH2:38])=[CH:23][CH:24]=2)[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1(C)C=CC=CC=1.CC(O)=O>[NH2:1][C:2]1[N:7]=[C:6]([CH:8]([NH:38][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[C:31]([NH:30][C:22]2[CH:21]=[C:20]3[C:25]([C:26]([CH3:28])([CH3:29])[CH2:27][N:18]([C:16]([O:15][C:11]([CH3:14])([CH3:12])[CH3:13])=[O:17])[CH2:19]3)=[CH:24][CH:23]=2)=[O:39])[CH3:9])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 135822701-(2-Aminopyrimidin-4-yl)ethan-1-oneHCID 695107067-(2-amino-benzoylamino)-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Product 1

HCID 59017468tert-Butyl 7-{2-[1-(2-amino-pyrimidin-4-yl)-ethylamino]-benzoylamino}-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 1-(2-amino-pyrimidin-4-yl)-ethanone (Step B, 200 mg, 1.46 mmol) in toluene (15 mL) was added, 7-(2-amino-benzoylamino)-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (Example 15, Step A)(288 mg, 0.73 mmol), and HOAc (3 drops). The resulting mixture was heated at 95° C. under N2 for 20 h. The reaction was cooled to RT and NaBH(OAc)3 (620 mg, 2.92 mmol) was added and reheated for 3 h. The reaction was cooled to RT, quenched with Na2CO3 solution (2 M, 5 mL), solvent was evaporated in vacuo. The residue was extracted with CHCl3. The organic layer was washed with saturated NaHCO3, water, brine, dried over MgSO4, and evaporated in vacuo. The crude solid was purified by chromatography on silica gel. Elution with CH2Cl2:MeOH (95:5) gave THE final compound. MS m/z: 517.3 (M+H). Calc'd. for C29H37N6O3-517.63.

Workup

  1. temperatureThe reaction was cooled to RT
  2. temperatureThe reaction was cooled to RT
  3. customquenched with Na2CO3 solution (2 M, 5 mL), solvent
  4. customwas evaporated in vacuo
  5. extractionThe residue was extracted with CHCl3
  6. washThe organic layer was washed with saturated NaHCO3, water, brine
  7. dry with materialdried over MgSO4
  8. customevaporated in vacuo
  9. customThe crude solid was purified by chromatography on silica gel
  10. washElution with CH2Cl2:MeOH (95:5)

Sources & evidence

ORD record
ord-3734428d9e3245d9b452f5a8cad0c344
Source dataset
uspto-grants-2007_12
Patent number
US07307088B2

Reaction notes

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