Trifluoroacetic acid → HCID 178493872, compound

HRID 536256Notes

Reaction equation

HRID 536256 reaction equation
C(OC(=O)[NH:7][C:8]1[N:13]=[CH:12][C:11]([C:14](=[O:44])[NH:15][C:16]2[N:25]3[CH2:26][CH2:27][N:28]=[C:24]3[C:23]3[CH:22]=[CH:21][C:20]([O:29][CH2:30][CH2:31][CH2:32][S:33]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)(=[O:35])=[O:34])=[C:19]([O:42][CH3:43])[C:18]=3[N:17]=2)=[CH:10][N:9]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl.CCN(CC)CC>[NH2:7][C:8]1[N:13]=[CH:12][C:11]([C:14]([NH:15][C:16]2[N:25]3[CH2:26][CH2:27][N:28]=[C:24]3[C:23]3[CH:22]=[CH:21][C:20]([O:29][CH2:30][CH2:31][CH2:32][S:33]([N:36]4[CH2:37][CH2:38][O:39][CH2:40][CH2:41]4)(=[O:35])=[O:34])=[C:19]([O:42][CH3:43])[C:18]=3[N:17]=2)=[O:44])=[CH:10][N:9]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178493871HCID 178493871, compound

Product 1

HCID 178493872HCID 178493872, compoundYield 121.5%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl[5-({7-methoxy-8-[3-(morpholin-4-ylsulfonyl)propoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl}carbamoyl)pyrimidin-2-yl]carbamate (Step 1, 150 mg 0.26 mmol) was dissolved in CH2Cl2 (15 mL) and TFA (0.16 mL, 2.1 mmol) was added dropwise. The mixture was stirred at rt over 2 d, after which 5 drops of Et3N were added causing a solid to precipitate. The mixture was stirred overnight, then the solvents removed under reduced pressure. The resulting residue was triturated in EtOAc (15 mL), collected by vacuum filtration and washed further with EtOAc (10 mL). This solid was then triturated in water (5 mL) collected by vacuum filtration and washed further with water (10 mL). High vacuum drying gave the title compound (172 mg, 92%): HPLC MS RT=0.87 min, MH+=545.2; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.21-2.26 (2H, m), 3.15-3.18 (4H, m), 3.24-3.29 (2H, m), 3.61-3.65 (4H, m), 3.99 (3H, s), 4.18-4.25 (2H, m), 4.37 (2H, t), 4.48-4.55 (2H, m), 7.44 (1H, d), 8.02 (1H, d), 9.06 (2H, s).

Workup

  1. customto precipitate
  2. stirringThe mixture was stirred overnight
  3. customthe solvents removed under reduced pressure
  4. customThe resulting residue was triturated in EtOAc (15 mL)
  5. filtrationcollected by vacuum filtration
  6. washwashed further with EtOAc (10 mL)
  7. customThis solid was then triturated in water (5 mL)
  8. filtrationcollected by vacuum filtration
  9. washwashed further with water (10 mL)
  10. customHigh vacuum drying

Sources & evidence

ORD record
ord-478d0b13b275412a8c83c105a3c4e0e9
Source dataset
uspto-grants-2014_10
Patent number
US08859572B2

Reaction notes

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