Trifluoroacetic acid → HCID 73056230, compound

HRID 2284420Notes

Reaction equation

HRID 2284420 reaction equation
[OH:1][C:2]([CH3:43])([CH3:42])[C:3]([NH:5][C:6]1[CH:7]=[C:8]([C:12]2[CH:21]=[C:20]3[C:15]([C:16]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)=[N:17][C:18]([C:22]4[CH:23]=[N:24][C:25]([NH:28]C(=O)OC(C)(C)C)=[N:26][CH:27]=4)=[N:19]3)=[CH:14][CH:13]=2)[CH:9]=[CH:10][CH:11]=1)=[O:4].FC(F)(F)C(O)=O>CO.C(Cl)Cl>[NH2:28][C:25]1[N:26]=[CH:27][C:22]([C:18]2[N:17]=[C:16]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[C:15]3[C:20](=[CH:21][C:12]([C:8]4[CH:7]=[C:6]([NH:5][C:3](=[O:4])[C:2]([OH:1])([CH3:43])[CH3:42])[CH:11]=[CH:10][CH:9]=4)=[CH:13][CH:14]=3)[N:19]=2)=[CH:23][N:24]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86710185HCID 86710185, compound

Product 1

HCID 73056230HCID 73056230, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

In a 25 mL round bottom flask, tert-butyl (5-(7-(3-(2-hydroxy-2-methylpropanamido)phenyl)-4-morpholinoquinazolin-2-yl)pyrimidin-2-yl)carbamate (0.06 g, 0.0001 mol) and DCM (10 mL) were added. To the flask was added trifluoroacetic acid (0.5 mL) and the reaction stirred at room temperature for 5 hours. The volatiles were evaporated under reduced pressure to provide the residue. The residue was dissolved in 5% methanol in DCM and washed with saturated sodium bicarbonate. The organic layer was washed with water, brine, dried over sodium sulfate and evaporated under reduced pressure to provide the crude product. The crude product was purified by preparative HPLC (10 mM NH4OAc and 1:1 MeOH:ACN) to obtain the title compound (0.007 mg, 14%). 1H NMR (DMSO-d6, 400 MHz): δ 9.76 (s, 1H), 9.22 (s, 2H), 8.32 (s, 1H), 8.11 (d, J=8.8 Hz, 1H), 8.05 (s, 1H), 7.87 (d, J=8.0 Hz, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.56 (d, J=7.6 Hz, 1H), 7.48 (t, J=8.8 Hz, 1H), 7.16 (s, 2H), 3.85 (s, 8H), 1.39 (s, 6H): LC-MS (ESI): Calculated mass. 485.2, Observed mass [M+H]+: 486.2. (RT=0.11 min).

Workup

  1. customThe volatiles were evaporated under reduced pressure
  2. customto provide the residue
  3. washwashed with saturated sodium bicarbonate
  4. washThe organic layer was washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated under reduced pressure
  7. customto provide the crude product
  8. customThe crude product was purified by preparative HPLC (10 mM NH4OAc and 1:1 MeOH:ACN)

Sources & evidence

ORD record
ord-7190550c11094fca8811ac3eac56c7e0
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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