Dichloromethane → HCID 86729521, compound

HRID 712522Notes

Reaction equation

HRID 712522 reaction equation
[N:1]1[N:2]=[CH:3][N:4]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=12.Cl[CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][C:24]=1[O:25][CH3:26])[N:21]=[CH:20][N:19]=[C:18]2[NH:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]#[CH:35])[CH:29]=1.C(Cl)Cl>CN(C=O)C>[N:1]1[N:2]=[CH:3][N:4]2[CH2:9][CH2:8][N:7]([CH2:11][CH2:12][CH2:13][O:14][C:15]3[CH:16]=[C:17]4[C:22](=[CH:23][C:24]=3[O:25][CH3:26])[N:21]=[CH:20][N:19]=[C:18]4[NH:27][C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([C:34]#[CH:35])[CH:29]=3)[CH2:6][C:5]=12

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 179987185H,6H,7H,8H-(1,2,4)triazolo(4,3-a)pyrazineHCID 867294706-(3-chloropropoxy)-N-(3-ethynylphenyl)-7-methoxyquinazolin-4-amine

Product 1

HCID 86729521HCID 86729521, compoundYield 20.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (0.17 g) in DMF (8 mL) was added Ag2CO3 (1.29 g) and a solution of 6-(3-chloropropoxy)-N-(3-ethynylphenyl)-7-methoxyquinazolin-4-amine (0.45 g) in DMF (2 mL) at room temperature under stirring. The mixture was stirred at 80° C. for 36 h under N2 and cooled to room temperature. To this, CH2Cl2 (100 mL) was added. The mixture was washed with brine (100 mL×3), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to give the product (114 mg, 20.50%), HPLC: 90.63%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 456.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.03-2.10 (m, 2H), 2.68 (t, J=13.20 Hz, 2H), 3.03 (t, J=10.80 Hz, 2H), 3.75 (s, 2H), 3.89 (s, 3H), 3.99 (s, 1H), 4.03 (t, J=10.80 Hz, 2H), 4.08 (t, J=12.40 Hz, 2H), 7.03 (m, 1H), 7.24 (s, 1H), 7.32 (m, 1H), 7.38 (s, 1H), 7.81-7.84 (m, 2H), 8.46 (s, 1H), 8.70 (s, 1H) ppm.

Workup

  1. temperaturecooled to room temperature
  2. washThe mixture was washed with brine (100 mL×3)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH)

Sources & evidence

ORD record
ord-23a67645db294e92b768cbebad1da74e
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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