Acetic Acid → HCID 11785433, compound

HRID 1592069Notes

Reaction equation

HRID 1592069 reaction equation
Cl.NO.[NH2:4][C:5]1[C:6]2[S:13][C:12]3[N:14]=[C:15]([N:21]4[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]4)[CH:16]=[C:17]([CH2:18][CH2:19][CH3:20])[C:11]=3[C:7]=2[N:8]=[CH:9][N:10]=1.[C:28]([BH3-])#[N:29].[C:31]([OH:34])(=O)[CH3:32].C[N:36]([CH:38]=[O:39])C>[OH-].[NH4+]>[NH2:4][C:5]1[C:6]2[S:13][C:12]3[N:14]=[C:15]([N:21]4[CH2:26][CH2:25][CH:24]([NH:29][CH2:28][CH:31]([C:32]5[CH:12]=[CH:11][C:7]([C:38]([NH2:36])=[O:39])=[CH:6][CH:5]=5)[OH:34])[CH2:23][CH2:22]4)[CH:16]=[C:17]([CH2:18][CH2:19][CH3:20])[C:11]=3[C:7]=2[N:8]=[CH:9][N:10]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 443297Hydroxyamine hydrochlorideHCID 498716Cyano-borohydrideHCID 11416569HCID 11416569, compound

Product 1

HCID 11785433HCID 11785433, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
90 °C

Procedure

The above amino alcohol HCl salt (1.00 g, 4.32 mmol) was suspended in ammonium hydroxide and heated in a stainless steel pressure vessel at 90° C. for 3 h. The solvent was removed in vacuo. The resulting free base was used without further purification. 1-(4-Amino-9-propyl-pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-7-yl)-piperidin-4-one (Example 4) (570 mg, 1.67 mmol) and the above amide (300 mg, 1.67 mmol) were dissolved in 10 mL of dry DMF. MP-Cyanoborohydride (0534 mg, 1.20 mmol) was added followed by 0.5 mL of glacial acetic acid. This mixture was shaken for 16 h. The resin was removed by filtration and washed with MeOH and dichloromethane. The filtrate was evaporated. The residue was treated with 2 M sodium carbonate solution. The resulting solid was collected by filtration and purified with flash chromatography (110 g SiO2, 10-20% EtOH/CH2Cl2 1% NH4OH, 50 mL/min, 100 minutes, UV detection at 254 nm) to give the title compound as a yellow solid (0.360 g, 49%).

Workup

  1. customThe solvent was removed in vacuo
  2. customThe resulting free base was used without further purification
  3. customThe resin was removed by filtration
  4. washwashed with MeOH and dichloromethane
  5. customThe filtrate was evaporated
  6. additionThe residue was treated with 2 M sodium carbonate solution
  7. filtrationThe resulting solid was collected by filtration
  8. custompurified with flash chromatography (110 g SiO2, 10-20% EtOH/CH2Cl2 1% NH4OH, 50 mL/min, 100 minutes, UV detection at 254 nm)

Sources & evidence

ORD record
ord-fe5d882fb1e6456db2ae13ae2fdf0327
Source dataset
uspto-grants-2007_11
Patent number
US07291733B2

Reaction notes

Loading…