Water → 4-oxo-N-(6-(pyrrolidin-1-ylmethyl)pyridin-2-yl)-2-(3-(trifluoromethyl)phenyl)-4H-chromene-8-carboxamide

HRID 876540Notes

Reaction equation

HRID 876540 reaction equation
CCN(C(C)C)C(C)C.[O:10]=[C:11]1[C:20]2[C:15](=[C:16]([C:21](Cl)=[O:22])[CH:17]=[CH:18][CH:19]=2)[O:14][C:13]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)=[CH:12]1.Cl.[N:35]1([CH2:40][C:41]2[N:46]=[C:45]([NH2:47])[CH:44]=[CH:43][CH:42]=2)[CH2:39][CH2:38][CH2:37][CH2:36]1.O>CC#N>[O:10]=[C:11]1[C:20]2[C:15](=[C:16]([C:21]([NH:47][C:45]3[CH:44]=[CH:43][CH:42]=[C:41]([CH2:40][N:35]4[CH2:39][CH2:38][CH2:37][CH2:36]4)[N:46]=3)=[O:22])[CH:17]=[CH:18][CH:19]=2)[O:14][C:13]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)=[CH:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 584773264-oxo-2-(3-(trifluoromethyl)phenyl)-4H-chromene-8-carbonyl chlorideHCID 672957736-(Pyrrolidin-1-ylmethyl)pyridin-2-amine hydrochloride

Product 1

HCID 584772604-oxo-N-(6-(pyrrolidin-1-ylmethyl)pyridin-2-yl)-2-(3-(trifluoromethyl)phenyl)-4H-chromene-8-carboxamideYield 40%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

DIPEA (125 mL, 0.705 mmol) was added to a solution of 4-oxo-2-(3-(trifluoromethyl)phenyl)-4H-chromene-8-carbonyl chloride 37 (83 mg, 0.235 mmol) and 6-(pyrrolidin-1-ylmethyl)pyridin-2-amine hydrochloride 49 (75 mg, 0.353 mmol) in CH3CN (15 mL). The reaction mixture was heated at 60° C. for 12 h, cooled to room temperature and poured into H2O. The mixture was extracted with CH2Cl2. The combined organics were dried (MgSO4) and concentrated. The crude residue was purified by MPLC eluting with CH2Cl2/MeOH (0-10%) to give Compound 243 (46 mg, 40% yield). MS (ESI) calcd for C27H22F3N3O3: 493.16. found: 494 [M+H].

Workup

  1. temperaturecooled to room temperature
  2. extractionThe mixture was extracted with CH2Cl2
  3. dry with materialThe combined organics were dried (MgSO4)
  4. concentrationconcentrated
  5. customThe crude residue was purified by MPLC
  6. washeluting with CH2Cl2/MeOH (0-10%)

Sources & evidence

ORD record
ord-14e86065c53b41069cb0314a66020b16
Source dataset
uspto-grants-2015_03
Patent number
US08987258B2

Reaction notes

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