Methanol → HCID 118061026, compound

HRID 575531Notes

Reaction equation

HRID 575531 reaction equation
[NH2:1][C:2]1[C:7]([CH2:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16](=[O:27])[C@@H:17]([NH:19]C(=O)OC(C)(C)C)[CH3:18])[CH2:12][CH2:11]2)=[C:6]([Cl:28])[N:5]=[C:4]([CH3:29])[N:3]=1.C(O)(C(F)(F)F)=O.CO.O>C(Cl)Cl>[NH2:19][C@@H:17]([CH3:18])[C:16]([N:13]1[CH2:14][CH2:15][CH:10]([CH2:9][CH2:8][C:7]2[C:2]([NH2:1])=[N:3][C:4]([CH3:29])=[N:5][C:6]=2[Cl:28])[CH2:11][CH2:12]1)=[O:27]

Participants

6

Reactant 4

HCID 887Methanol2×HCID 962WaterHCID 6422Trifluoroacetic acidHCID 118061845HCID 118061845, compound

Product 1

HCID 118061026HCID 118061026, compoundYield 85.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve tert-butyl N-[(1S)-2-[4-[2-(4-amino-6-chloro-2-methyl-pyrimidin-5-yl)ethyl]-1-piperidyl]-1-methyl-2-oxo-ethyl]carbamate (15.78 g, 37.05 mmol) in DCM (185 mL), add TFA (185 mL) in a dropwise manner over 3 min, and stir overnight. Analyze the reaction by LCMS (low pH) to show complete conversion. Slowly add MeOH (400 mL) due to exothermic mixing. Prewash three SCX columns (50 g) with water (20 mL) and then MeOH (20 mL). Divide the reaction mixture into three equal portions and load equally onto the SCX columns Wash each column with water (40 mL) and MeOH (40 mL) collecting the washes in a vacuum flask. Elute the desired material from the SCX columns with 2 N ammonia in MeOH (60 mL) into a clean vessel. Combine the product containing solutions, concentrate under reduced pressure, azeotrope with DCM-hexanes (1:1), three times, and place under vacuum to obtain the title compound as a white foam (10.29 g, 84%). LC-ES/MS m/z (35Cl/37Cl) 326.2/328.2 (M+1).

Workup

  1. customthe reaction by LCMS (low pH)
  2. washWash each column with water (40 mL) and MeOH (40 mL)
  3. customcollecting the washes in a vacuum flask
  4. washElute the desired material from the SCX columns with 2 N ammonia in MeOH (60 mL) into a clean vessel
  5. additioncontaining solutions
  6. concentrationconcentrate under reduced pressure, azeotrope with DCM-hexanes (1:1), three times, and place under vacuum

Sources & evidence

ORD record
ord-a9fc4a05c456481c86fdbbccb8523bd9
Source dataset
uspto-grants-2015_05
Patent number
US09035051B1

Reaction notes

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