3-Methyl-2-furoic acid → US9296747, Example 11

HRID 930509Notes

Reaction equation

HRID 930509 reaction equation
N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[CH3:28][C:29]1[CH:33]=[CH:32][O:31][C:30]=1[C:34]([OH:36])=O.C(N(C(C)C)CC)(C)C.[CH3:46][O:47][C:48]1[CH:49]=[C:50]([NH:58][C:59]2[N:60]=[CH:61][C:62]3[CH2:68][NH:67][CH2:66][CH2:65][C:63]=3[N:64]=2)[CH:51]=[C:52]([O:56][CH3:57])[C:53]=1[O:54][CH3:55]>CN(C=O)C.CCOC(C)=O>[CH3:28][C:29]1[CH:33]=[CH:32][O:31][C:30]=1[C:34]([N:67]1[CH2:66][CH2:65][C:63]2[N:64]=[C:59]([NH:58][C:50]3[CH:49]=[C:48]([O:47][CH3:46])[C:53]([O:54][CH3:55])=[C:52]([O:56][CH3:57])[CH:51]=3)[N:60]=[CH:61][C:62]=2[CH2:68]1)=[O:36]

Participants

7

Reactant 4

HCID 781273-Methyl-2-furoic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 118970894N-(3,4,5-Trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine

Product 1

HCID 118970899US9296747, Example 11Yield 47.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium-hexafluorophosphate (0.035 g, 0.079 mmol) in anhydrous DMF (2 mL) was treated sequentially with 3-methylfuran-2-carboxylic acid (0.013 g, 0.103 mmol) and diisopropylethylamine (0.035 mL, 0.159 mmol). The reaction mixture was allowed to stir for 30 minutes at room temperature. After 30 minutes, N-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-amine, Intermediate 1 (0.025 g, 0.079 mmol) was added to the reaction mixture. The reaction was allowed to stir for 3 hours at room temperature. The reaction mixture was then diluted with EtOAc and washed three times with brine. The combined aqueous layers were then washed twice with EtOAc. The organic layers were combined, dried over anhydrous Na2SO4(s), filtered and concentrated in vacuo. The crude product was then purified over silica using a MeOH/CHCl3 gradient affording the final product in 47.3% yield (0.014 g, 0.037 mmol).

Workup

  1. waitAfter 30 minutes
  2. stirringto stir for 3 hours at room temperature
  3. washwashed three times with brine
  4. washThe combined aqueous layers were then washed twice with EtOAc
  5. dry with materialdried over anhydrous Na2SO4(s)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was then purified over silica using a MeOH/CHCl3 gradient

Sources & evidence

ORD record
ord-b367f269be634e92a4a5a9e305a3c1bc
Source dataset
uspto-grants-2016_03
Patent number
US09296747B1

Reaction notes

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