Tert-Butylamine → HCID 89782141, compound

HRID 1056432Notes

Reaction equation

HRID 1056432 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9](Cl)[N:8]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:7]2=[O:19].[CH3:20][C:21]([NH2:24])([CH3:23])[CH3:22]>CN1C(=O)CCC1.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:24][C:21]([CH3:23])([CH3:22])[CH3:20])[N:8]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:7]2=[O:19]

Participants

5

Reactant 2

HCID 6385Tert-ButylamineHCID 89782177HCID 89782177, compound

Product 1

HCID 89782141HCID 89782141, compoundYield 12.4%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 8-bromo-2-chloro-3-(tetrahydro-2H-pyran-4-yl)quinazolin-4(3H)-one (515c, 0.51 g, 1.484 mmol) and 2-methylpropan-2-amine (Sigma-Aldrich Co., 3.12 mL, 29.7 mmol) in NMP (7.42 mL) was stirred at 100° C. for 16 h. The reaction mixture was diluted with EtOAc (100 mL), added to a separatory funnel, and washed with water (3×100 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 100% hexanes to 60% EtOAc in hexanes to give 8-bromo-2-(tert-butylamino)-3-(tetrahydro-2H-pyran-4-yl)quinazolin-4(3H)-one (515d, 70 mg, 0.184 mmol, 12.40% yield) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.63 (s, 9H) 1.77 (dd, J=12.52, 2.54 Hz, 2H) 2.41 (qd, J=12.52, 4.69 Hz, 2H) 3.58 (td, J=11.74, 1.96 Hz, 2H) 4.14 (dd, J=12.23, 4.21 Hz, 2H) 4.70 (s, 1H) 5.48 (t, J=12.72 Hz, 1H) 6.97 (t, J=7.82 Hz, 1H) 7.83 (dd, J=7.63, 1.37 Hz, 1H) 8.04 (dd, J=8.02, 1.37 Hz, 1H). MS (ESI, pos. ion) m/z: 380.2/382.2 (M+1).

Workup

  1. additionadded to a separatory funnel
  2. washwashed with water (3×100 mL)
  3. customthe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customwas purified

Sources & evidence

ORD record
ord-654175ce160d41e5b193bb8ec7cca8cf
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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