Diisopropylethylamine → HCID 23633265, compound

HRID 2039676Notes

Reaction equation

HRID 2039676 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][CH3:9])[CH:3]=1.Cl[C:11](Cl)([O:13]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(C(C)C)CC)(C)C.[CH3:31][NH:32][C:33]([C:35]1[CH:40]=[C:39]([O:41][C:42]2[CH:47]=[CH:46][C:45]([NH2:48])=[C:44]([F:49])[CH:43]=2)[CH:38]=[CH:37][N:36]=1)=[O:34]>C1COCC1.CN(C=O)C>[CH3:31][NH:32][C:33]([C:35]1[CH:40]=[C:39]([O:41][C:42]2[CH:47]=[CH:46][C:45]([NH:48][C:11]([NH:1][C:2]3[CH:3]=[C:4]([O:8][CH3:9])[N:5]=[CH:6][N:7]=3)=[O:13])=[C:44]([F:49])[CH:43]=2)[CH:38]=[CH:37][N:36]=1)=[O:34]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 7357314-Amino-6-methoxypyrimidineHCID 468352194-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide

Product 1

HCID 23633265HCID 23633265, compoundYield 24.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 6-amino-4-methoxypyrimidine (50.0 mg; 0.39 mmol), triphosgene (43.0 mg; 0.14 mmol) and diisopropylethylamine (60.7 mg; 0.47 mmol) in THF (2.0 mL) was heated at 70° C. for 4 h. A solution of 4-(4-amino-3-fluoro-phenoxy)-pyridine-2-carboxylic acid methylamide (102.3 mg; 0.39 mmol) in DMF (1.0 mL) was then added, and the reaction mixture was heated at 70° C. for another 8 h, then extracted between EtOAc and saturated aqueous NaHCO3. The organic layer was dried and evaporated to give a crude oil that was purified via HPLC to give the title compound (14 mg, 9%). 1H-NMR (CD3OD) δ 8.36 (s, 1H), 8.35 (s, 1H), 8.14 (t, J=8.8 Hz, 1H), 7.46 (d, J=2.4 Hz, 1H), 7.00-6.86 (m, 3H), 6.60 (s, 1H), 3.86 (s, 3H), 2.83 (s, 3H); LC-MS m/z 413 [M+H]+.

Workup

  1. extractionextracted between EtOAc and saturated aqueous NaHCO3
  2. customThe organic layer was dried
  3. customevaporated
  4. customto give a crude oil that
  5. customwas purified via HPLC

Sources & evidence

ORD record
ord-e7406553d36f4630a33bb86f0ca3e831
Source dataset
uspto-grants-2013_11
Patent number
US08580798B2

Reaction notes

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