Triethylamine → N-(2,4-difluorophenyl)-N,8-dimethyl-4H-thieno[3,2-c]chromene-2-carboxamide

HRID 84712Notes

Reaction equation

HRID 84712 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[O:8][CH2:7][C:6]3[CH:12]=[C:13]([C:15]([OH:17])=O)[S:14][C:5]=3[C:4]=2[CH:3]=1.[CH3:18][NH:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[F:27].C(N(CC)CC)C>ClCCl.CN(C1C=CN=CC=1)C>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[N:19]([CH3:18])[C:15]([C:13]1[S:14][C:5]2[C:4]3[CH:3]=[C:2]([CH3:1])[CH:11]=[CH:10][C:9]=3[O:8][CH2:7][C:6]=2[CH:12]=1)=[O:17]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27370232,4-difluoro-N-methylanilineHCID 579005248-methyl-4H-thieno[3,2-c]chromene-2-carboxylic acid

Product 1

HCID 57900253N-(2,4-difluorophenyl)-N,8-dimethyl-4H-thieno[3,2-c]chromene-2-carboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

8-Methyl-4H-thieno[3,2-c]chromene-2-carboxylic acid was converted to the acid chloride as in Example 3, then treated with N-methyl-2,4-difluoroaniline (1.5 equiv), and triethylamine (5 equiv) in dichloromethane and N,N-dimethyl-4-aminopyridine (0.2 equiv) at 24° C. After about 24 hr, the reaction mixture was diluted with dichloromethane, and the resulting solution was washed with saturated aqueous sodium bicarbonate. The collected organic was dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (5:2 hexanes/ethylacetate) provided 167bp. 1H NMR (500 MHz, CDCl3) δ 7.29 (m, 1 H), 6.95-6.98 (m, 4 H,), 6.78 (d, J=8.2 Hz, 1 H), 5.04 (s, 2 H), 3.39 (s, 3 H), 2.27 (s, 3 H). LCMS (ESI) m/z: 372.1.

Workup

  1. washthe resulting solution was washed with saturated aqueous sodium bicarbonate
  2. dry with materialThe collected organic was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash column chromatography (5:2 hexanes/ethylacetate)
  6. customprovided 167bp

Sources & evidence

ORD record
ord-121361e57eb545688ae213ad84e2044e
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Reaction notes

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