4-Chloroquinazoline → HCID 58770778, compound

HRID 657195Notes

Reaction equation

HRID 657195 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH3:12][O:13][C:14]([CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1)=[O:15].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1COCC1>>[CH3:12][O:13][C:14]([C:16]1([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21]1)=[O:15]

Participants

4

Reactant 3

HCID 788644-ChloroquinazolineHCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl esterHCID 23714775LiHMDS tetrahydrofuran

Product 1

HCID 58770778HCID 58770778, compoundYield 109%

Procedure

A mixture of 4-chloroquinazoline (2.02 g, 12.3 mmol), prepared as described in the preceding step, and piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (3.13 g, 12.8 mmol), as prepared in Example 1b, was treated with 1.08 M LiHMDS/THF in one portion by syringe at 0° C. with stirring under argon. After stirring for an additional 5 min at 0° C., the ice bath was removed and the homogeneous amber solution was stirred at rt for 4.5 h. The reaction was quenched with 1 M NaH2PO4 (30 mL) and extracted with DCM (2×30 mL). The organic layers were combined, dried (Na2SO4), and concentrated under reduced pressure to give the crude title compound as a clear amber syrup (4.98 g). 1H-NMR (300 MHz, CDCl3) δ 9.29 (s, 1H), 8.06 (m, 2H), 7.87 (m, 1H), 7.59 (m, 1H), 3.72-3.52 (m, 4H), 3.60 (s, 3H), 2.50-2.40 (br m, 4H), 1.46 (s, 9H). LC/MS (ESI): calcd mass 371.2, found 372.2 (MH)+.

Workup

  1. customprepared
  2. customas prepared in Example 1b
  3. stirringAfter stirring for an additional 5 min at 0° C.
  4. customthe ice bath was removed
  5. stirringthe homogeneous amber solution was stirred at rt for 4.5 h
  6. customThe reaction was quenched with 1 M NaH2PO4 (30 mL)
  7. extractionextracted with DCM (2×30 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3bc8d2c6c3e8447b851b130c19c2834e
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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