HCID 67298312, compound → HCID 67298435, compound

HRID 1520322Notes

Reaction equation

HRID 1520322 reaction equation
[C:1]([Si:5]([CH3:36])([CH3:35])[O:6][CH2:7][C:8]#[C:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)[N:14]=[C:13]2[NH:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[C:29]([Cl:34])[CH:28]=1)([CH3:4])([CH3:3])[CH3:2]>CCOC(C)=O.CO>[Si:5]([O:6][CH2:7][CH2:8][CH2:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)[N:14]=[C:13]2[NH:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[C:29]([Cl:34])[CH:28]=1)([C:1]([CH3:4])([CH3:2])[CH3:3])([CH3:36])[CH3:35]

Participants

4

Reactant 1

HCID 67298312HCID 67298312, compound

Product 1

HCID 67298435HCID 67298435, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 6-(3-(tert-butyldimethyl silyloxy)prop-1-ynyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (0.20 g, 0.39 mmol) and 5% Pd—S—C (40 mg) in EtOAc (5 mL) and MeOH (5 mL) was stirred overnight at room temperature under hydrogen atmosphere. The reaction mixture was filtered through Celite. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluted with hexane/ethyl acetate 6:1 to 2:3) to give 0.15 g of 6-(3-(tert-butyldimethylsilyloxy)propyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine as yellow solid (74%). LCMS m/z=523 (M+1) (Method D) (retention time=3.35 min). 1H NMR (300 MHz, CDCl3) δ 9.69 (dd, J=2.2, 0.8 Hz, 1H), 8.79-8.65 (m, 2H), 8.07 (dd, J=6.5, 2.7 Hz, 1H), 7.94 (d, J=8.5 Hz, 1H), 7.76-7.61 (m, 3H), 7.47-7.37 (m, 2H), 7.31-7.18 (m, 1H), 3.68 (t, J=6.1 Hz, 2H), 3.01-2.83 (m, 2H), 2.03-1.86 (m, 2H), 0.94 (s, 9H), 0.08 (s, 6H).

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationThe filtrate was concentrated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (eluted with hexane/ethyl acetate 6:1 to 2:3)

Sources & evidence

ORD record
ord-c50678e64b5b43a5b9061725ed528fa7
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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