Triethylamine → HCID 59597015, compound

HRID 2066287Notes

Reaction equation

HRID 2066287 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2([C:14]([OH:16])=O)[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:48][C:49]1[CH:54]=[C:53]([O:55][C:56]2[CH:61]=[C:60]([F:62])[C:59]([NH2:63])=[CH:58][C:57]=2[F:64])[N:52]=[CH:51][N:50]=1>CN(C)C=O>[NH2:48][C:49]1[CH:54]=[C:53]([O:55][C:56]2[C:57]([F:64])=[CH:58][C:59]([NH:63][C:14]([C:11]3([C:9]([NH:8][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[O:10])[CH2:12][CH2:13]3)=[O:16])=[C:60]([F:62])[CH:61]=2)[N:52]=[CH:51][N:50]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 210815301-[(4-Fluorophenyl)carbamoyl]cyclopropanecarboxylic AcidHCID 57470876HCID 57470876, compound

Product 1

HCID 59597015HCID 59597015, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1-(4-fluorophenylaminocarbonyl)cyclopropanecarboxylic acid (378 mg) in N,N-dimethylformamide (3 ml) were added triethylamine (0.236 ml) and HATU (644 mg) at room temperature under a nitrogen atmosphere, followed by stirring for 30 min. To the resultant mixture was added 4-amino-6-(4-amino-2,5-difluorophenoxy)pyrimidine (270 mg) in N,N-dimethylformamide (3 ml) at room temperature, followed by stirring for 6 hr. Triethylamine (0.079 ml) and HATU (215 mg) were added again and the resultant mixture was stirred overnight. The reaction mixture was partitioned between ethyl acetate (20 ml) and a 1N aqueous solution of sodium hydroxide (10 ml). The organic layer was washed with a 1N aqueous solution of sodium hydroxide (10 ml, twice) and brine (10 ml), dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure and the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:2 to 1:4). Fractions containing the target compound were concentrated under reduced pressure and the residue was dried under reduced pressure to provide the titled compound as pale brown powder (199 mg, 40%).

Workup

  1. stirringby stirring for 6 hr
  2. customThe reaction mixture was partitioned between ethyl acetate (20 ml)
  3. washThe organic layer was washed with a 1N aqueous solution of sodium hydroxide (10 ml
  4. dry with materialtwice) and brine (10 ml), dried over anhydrous sodium sulfate
  5. concentrationThe solvent was concentrated under reduced pressure
  6. customthe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:2 to 1:4)
  7. additionFractions containing the target compound
  8. concentrationwere concentrated under reduced pressure
  9. customthe residue was dried under reduced pressure

Sources & evidence

ORD record
ord-e11ee751a17b40b382b40953d19d160a
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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