Formamide → 5-(2-Phenylquinolin-7-yl)-thieno[2,3-d]pyrimidin-4-ylamine

HRID 230237Notes

Reaction equation

HRID 230237 reaction equation
C1([C:7]2C=CC3C(=CC(C(=O)C)=CC=3)[N:8]=2)C=CC=CC=1.C(#N)CC#N.[S].N1CCOCC1.[CH:32]([NH2:34])=O.[NH2:35][C:36]1[S:37][CH:38]=[C:39]([C:43]2[CH:52]=[C:51]3[C:46]([CH:47]=[CH:48][C:49]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)=[N:50]3)=[CH:45][CH:44]=2)[C:40]=1C#N>[Cl-].[Na+].O>[C:53]1([C:49]2[CH:48]=[CH:47][C:46]3[C:51](=[CH:52][C:43]([C:39]4[C:40]5[C:32]([NH2:34])=[N:8][CH:7]=[N:35][C:36]=5[S:37][CH:38]=4)=[CH:44][CH:45]=3)[N:50]=2)[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1

Participants

8

Reactant 6

HCID 713FormamideHCID 8010MalononitrileHCID 8083MorpholineHCID 5362487SulfurHCID 577623782-Amino-4-(2-phenylquinolin-7-yl)-thiophene-3-carbonitrileHCID 577623961-(2-Phenylquinolin-7-yl)-ethanone2×

Product 1

HCID 160687065-(2-Phenylquinolin-7-yl)-thieno[2,3-d]pyrimidin-4-ylamine

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

One-pot synthesis from 1-(2-phenylquinolin-7-yl)-ethanone: The mixture of 1-(2-phenylquinolin-7-yl)-ethanone (50 mg, 0.20 mmol), malononitrile (40 mg, 0.60 mmol), sulfur (39 mg, 1.2 mmol), morpholine (0.12 ml), and formamide (1.0 ml) in a sealed tube was heated at 80° C. for 17 h under N2. LC-MS confirmed the formation of 2-amino-4-(2-phenylquinolin-7-yl)-thiophene-3-carbonitrile (MS (ES+): m/z 328.1 (100) [MH+]). The above mixture was then heated to 180° C. for 3 h. The cooled reaction mixture was poured into brine (10 ml) and extracted with EtOAc (3×15 ml). The combined organic extracts were washed with brine (10 ml), dried over MgSO4, filtered, and concentrated to give a brown oil. Purification by TLC on silica gel [eluting with EtOAc/hexane (40/60)], followed by HPLC gave the title compound as an off-white solid.

Workup

  1. temperatureThe above mixture was then heated to 180° C. for 3 h
  2. customThe cooled reaction mixture
  3. extractionextracted with EtOAc (3×15 ml)
  4. washThe combined organic extracts were washed with brine (10 ml)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a brown oil
  9. customPurification by TLC on silica gel [eluting with EtOAc/hexane (40/60)]

Sources & evidence

ORD record
ord-caaa94ca453a4ebfaa1fc899c009bd6e
Source dataset
uspto-grants-2009_07
Patent number
US07566721B2

Reaction notes

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