Hydrochloric Acid → 7-[3-(4-Methyl-piperazin-1-yl)-propoxy]-4-piperidin-4-yl-quinazoline

HRID 657250Notes

Reaction equation

HRID 657250 reaction equation
CC([O-])(C)C.[K+].C(OC([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[CH:27][CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH2:16][CH2:15]1)=O)(C)(C)C.[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][CH2:40][OH:41])[CH2:34][CH2:33]1.Cl.[OH-].[Na+]>C1COCC1.C(Cl)Cl.CO>[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][CH2:40][O:41][C:26]2[CH:25]=[C:24]3[C:29]([C:20]([CH:17]4[CH2:16][CH2:15][NH:14][CH2:19][CH2:18]4)=[N:21][CH:22]=[N:23]3)=[CH:28][CH:27]=2)[CH2:34][CH2:33]1

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 792083-(4-Methyl-1-piperazine)propan-1-olHCID 23665647Potassium tert-butoxide2×HCID 595517364-(7-Fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 120037067-[3-(4-Methyl-piperazin-1-yl)-propoxy]-4-piperidin-4-yl-quinazolineYield 108%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

Solid KOtBu (1.36 g, 12.1 mmol) was added in one portion under air to a homogeneous solution of 4-(7-Fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (3.33 g, 10.1 mmol), as prepared in the preceding step, and commercial 3-(4-methyl-piperazin-1-yl)-propan-1-ol (1.50 g, 9.50 mmol) in dry THF (10 mL), while stirring on an ice bath. Following KOtBu addition, the ice bath was immediately removed, and the resulting homogeneous amber solution was stirred for 6 hr. 6 M aqueous HCl (10 mL, 60 mmol) was then added in one portion, and the reaction was stirred overnight (mild bubbles were seen following HCl addition, but these subsided after 15 min). The reaction was then partitioned with 9:1 DCM/MeOH (50 mL) and 2.5 M NaOH (28 mL, 70 mmol), and the aqueous layer was extracted with 9:1 DCM/MeOH (1×50 mL). The combined organic layers were dried (Na2SO4) and concentrated by rotary evaporation at 90° C. to provide the crude title compound as a clear yellow oil (3.79 g, “102%” crude yield). LC/MS (ESI): calcd mass 369.3, found 370.2 (MH)+.

Workup

  1. customthe ice bath was immediately removed
  2. stirringthe resulting homogeneous amber solution was stirred for 6 hr
  3. stirringthe reaction was stirred overnight (mild bubbles
  4. extractionthe aqueous layer was extracted with 9:1 DCM/MeOH (1×50 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. concentrationconcentrated by rotary evaporation at 90° C.

Sources & evidence

ORD record
ord-d6338e409d8f4c02b98e7c972d735d4c
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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