Trifluoroacetic acid → HCID 46182696, compound

HRID 450541Notes

Reaction equation

HRID 450541 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]2[C:34]3[C:41]([CH3:42])=[C:40]([C:43]([O:45]C)=O)[S:39][C:35]=3[N:36]=[CH:37][N:38]=2)=[C:28]([O:47][CH:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)[CH:27]=1.CCN(C(C)C)C(C)C.[NH2:63][CH2:64][CH2:65][CH2:66][NH:67]C(=O)OC(C)(C)C.FC(F)(F)C(O)=O>CN(C=O)C.C(Cl)Cl>[NH2:63][CH2:64][CH2:65][CH2:66][NH:67][C:43]([C:40]1[S:39][C:35]2[N:36]=[CH:37][N:38]=[C:33]([NH:32][C:29]3[CH:30]=[CH:31][C:26]([F:25])=[CH:27][C:28]=3[O:47][CH:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)[C:34]=2[C:41]=1[CH3:42])=[O:45]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2735700tert-Butyl (3-aminopropyl)carbamateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 461820444-[4-Fluoro-2-(tetrahydro-pyran-4-yloxy)-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methylester

Product 1

HCID 46182696HCID 46182696, compoundYield 60.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

HATU (0.073 g, 0.193 mmol) was added into a mixture of methyl 4-(4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (0.07 g, 0.175 mmol) and Hünig's base (30 μL, 0.175 mmol) in DMF (2.0 mL) at 0° C. The reaction mixture was stirred at 0° C. for 0.5 hours. tert-Butyl 3-aminopropylcarbamate (0.152 g, 0.875 mmol) was added, the coolant removed and the reaction stirred at ambient temperature overnight. The product was recrystallised from EtOAc to yield colourless solid. The solid was dissolved in DCM (2.0 mL), treated with trifluoroacetic acid (0.50 mL) and the reaction stirred at ambient temperature for 2 hours. The reaction mixture was applied to an SCX cartridge and eluted with MeOH (30 mL) followed by ammonia in MeOH to elute the product. Evaporation of appropriate fractions gave the product as a colourless solid (0.049 g, 60%).

Workup

  1. customthe coolant removed
  2. stirringthe reaction stirred at ambient temperature overnight
  3. customThe product was recrystallised from EtOAc
  4. customto yield colourless solid
  5. stirringthe reaction stirred at ambient temperature for 2 hours
  6. washeluted with MeOH (30 mL)
  7. washto elute the product
  8. customEvaporation of appropriate fractions

Sources & evidence

ORD record
ord-d4c26ae45cd94acd94917848e1bad1bd
Source dataset
uspto-grants-2013_07
Patent number
US08486953B2

Reaction notes

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