Carbon Tetrachloride → (R)-N,N-dimethyl-2-(4-(1-(thiazol-4-ylmethyl)-1H-indazol-5-ylamino)quinazolin-5-yloxy)propanamide

HRID 1162228Notes

Reaction equation

HRID 1162228 reaction equation
[CH3:1][N:2]([CH3:19])[C:3](=[O:18])[C@H:4]([O:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[C:9](=O)[NH:10][CH:11]=[N:12]2)[CH3:5].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)Cl.[S:44]1[CH:48]=[C:47]([CH2:49][N:50]2[C:58]3[C:53](=[CH:54][C:55]([NH2:59])=[CH:56][CH:57]=3)[CH:52]=[N:51]2)[N:46]=[CH:45]1>ClCCCl>[CH3:1][N:2]([CH3:19])[C:3](=[O:18])[C@H:4]([O:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[C:9]([NH:59][C:55]1[CH:54]=[C:53]3[C:58](=[CH:57][CH:56]=1)[N:50]([CH2:49][C:47]1[N:46]=[CH:45][S:44][CH:48]=1)[N:51]=[CH:52]3)=[N:10][CH:11]=[N:12]2)[CH3:5]

Participants

6

Reactant 4

HCID 5943Carbon TetrachlorideHCID 11776TriphenylphosphineHCID 686176261-[(1,3-Thiazol-4-yl)methyl]-1H-indazol-5-amineHCID 136346624(2R)-N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamide

Product 1

HCID 16117347(R)-N,N-dimethyl-2-(4-(1-(thiazol-4-ylmethyl)-1H-indazol-5-ylamino)quinazolin-5-yloxy)propanamideYield 60%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of (2R)—N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamide (200 mg, 0.77 mmol), triphenylphosphine (603 mg, 2.3 mmol) and carbon tetrachloride (2.2 ml, 23 mmol) in 1,2-dichloroethane (5 ml) was stirred at 45° C. for 2 hours. 1-(1,3-Thiazol-4-ylmethyl)-1H-indazol-5-amine (184 mg, 0.8 mmol) was added and the solvents were evaporated under vacuum. Acetonitrile (5 ml) was added. The mixture was stirred at 75° C. for 2 hours. After cooling, the solvents were evaporated under vacuum. The residue was diluted in 6N methanolic ammonia and the solvents were evaporated under vacuum. The residue was purified by chromatography on silica gel (eluant: 3% to 5% methanol in DCM) to give the title compound as a beige foam (215 mg, 60%); NMR Spectrum (CDCl3) 1.73 (d, 3H), 3.06 (s, 3H), 3.14 (s, 3H), 5.43 (q, 1H), 5.80 (s, 2H), 6.81 (d, 1H), 6.93 (s, 1H), 7.48 (m, 2H), 7.60 (t, 1H), 7.84 (dd, 1H), 8.08 (s, 1H), 8.43 (s, 1H), 8.62 (s, 1H), 8.78 (s, 1H); Mass spectrum 474.

Workup

  1. customthe solvents were evaporated under vacuum
  2. additionAcetonitrile (5 ml) was added
  3. stirringThe mixture was stirred at 75° C. for 2 hours
  4. temperatureAfter cooling
  5. customthe solvents were evaporated under vacuum
  6. additionThe residue was diluted in 6N methanolic ammonia
  7. customthe solvents were evaporated under vacuum
  8. customThe residue was purified by chromatography on silica gel (eluant: 3% to 5% methanol in DCM)

Sources & evidence

ORD record
ord-ef02f22c132a48a4884e9544a5cec33b
Source dataset
uspto-grants-2010_10
Patent number
US07820683B2

Reaction notes

Loading…