Sodium hydride → HCID 178493897, compound

HRID 1259510Notes

Reaction equation

HRID 1259510 reaction equation
[H-].[Na+].FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[OH:17][C:18]1[CH:19]=[CH:20][C:21]2[C:22]3[N:23]([CH2:39][CH2:40][N:41]=3)[C:24]([NH:30][C:31]([C:33]3[CH:34]=[N:35][CH:36]=[N:37][CH:38]=3)=[O:32])=[N:25][C:26]=2[C:27]=1[O:28][CH3:29].Cl.Cl[CH2:44][CH2:45][N:46]([CH3:48])[CH3:47]>CN(C=O)C>[CH3:47][N:46]([CH3:48])[CH2:45][CH2:44][O:17][C:18]1[CH:19]=[CH:20][C:21]2[C:22]3[N:23]([CH2:39][CH2:40][N:41]=3)[C:24]([NH:30][C:31]([C:33]3[CH:34]=[N:35][CH:36]=[N:37][CH:38]=3)=[O:32])=[N:25][C:26]=2[C:27]=1[O:28][CH3:29]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochloride2×HCID 178493834HCID 178493834, compound

Product 1

HCID 178493897HCID 178493897, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (865 mg, 22 mmol, 60% dispersion in mineral oil) was diluted in DMF (35 mL). N-(8-Hydroxy-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyrimidine-5-carboxamide bis(trifluoroacetate) (1.75 g, 3.1 mmol) was added, followed by 2-chloro-N,N-dimethylethanamine hydrochloride (890 mg, 6.2 mmol). The reaction mixture was stirred at rt until gas evolution ceased and then was heated to 50° C. for 2 h. At this time, the mixture was cooled to rt, and an additional equivalent of 2-chloro-N,N-dimethylethanamine hydrochloride (445 mg, 3.1 mmol) was added. The resulting reaction mixture was stirred at 50° C. overnight. After cooling to rt, the excess sodium hydride was carefully quenched by the addition of water and the mixture was extracted several times with DCM. The combined organic layers were dried (sodium sulfate) and concentrated under reduced pressure. The resultant solid was triturated with EtOAc and hexanes to afford the title compound as a solid (710 mg, 56%): HPLC MS RT=1.09 min, MH+=410.1; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 9.47 (2H, s), 9.39 (1H, s), 8.12 (1H, d), 7.52 (1H, d), 4.61 (4H, m), 4.26 (2H, m), 4.03 (3H, s), 3.67 (2H, br t), 2.93 (6H, s).

Workup

  1. temperaturewas heated to 50° C. for 2 h
  2. temperatureAt this time, the mixture was cooled to rt
  3. customThe resulting reaction mixture
  4. stirringwas stirred at 50° C. overnight
  5. temperatureAfter cooling to rt
  6. customthe excess sodium hydride was carefully quenched by the addition of water
  7. extractionthe mixture was extracted several times with DCM
  8. dry with materialThe combined organic layers were dried (sodium sulfate)
  9. concentrationconcentrated under reduced pressure
  10. customThe resultant solid was triturated with EtOAc and hexanes

Sources & evidence

ORD record
ord-6cce1912faba44eca00466a362cdd2be
Source dataset
uspto-grants-2013_06
Patent number
US08466283B2

Reaction notes

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