Diisopropylethylamine → HCID 44199702, compound

HRID 2061180Notes

Reaction equation

HRID 2061180 reaction equation
[CH3:1][O:2][C@@H:3]([CH3:7])[C:4]([OH:6])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:41][N:42]1[C:51]2[C:46](=[CH:47][N:48]=[C:49]([CH3:52])[CH:50]=2)[CH:45]=[C:44]([C:53]2[CH:54]=[C:55]([NH:60]/[C:61](/[NH2:64])=[N:62]/O)[CH:56]=[CH:57][C:58]=2[CH3:59])[C:43]1=[O:65]>CN(C=O)C>[CH3:1][O:2][C@H:3]([C:4]1[O:6][N:62]=[C:61]([NH:60][C:55]2[CH:56]=[CH:57][C:58]([CH3:59])=[C:53]([C:44]3[C:43](=[O:65])[N:42]([CH3:41])[C:51]4[C:46]([CH:45]=3)=[CH:47][N:48]=[C:49]([CH3:52])[CH:50]=4)[CH:54]=2)[N:64]=1)[CH3:7]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 57025662-methoxypropanoic acid, (S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178422078HCID 178422078, compound2×

Product 1

HCID 44199702HCID 44199702, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (S)-2-methoxypropanoic acid (40 mg, 0.4 mmol) in DMF (4 mL) were added DIPEA (65 μL, 0.4 mmol) and HATU (0.14 g, 0.4 mmol). After stirring at rt for 15 min, 17 (0.13 g, 0.4 mmol) was added as a solution in DMF (1 mL). The reaction was stirred at rt until complete consumption of 17 was determined by LC/MS and then was heated at 100° C. for 3 h. Subsequently, the reaction was cooled to rt, partitioned with EtOAc (30 mL) and 5% aq NaHCO3 (20 mL). The aqueous layer was extracted with fresh EtOAc (2×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and reduced to dryness. The crude material was purified by flash column chromatography on silica with DCM/2% MeOH as eluant to give (S)-3-(5-(5-(1-methoxyethyl)-1,2,4-oxadiazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one (A76) as a clear white glassy solid. 1H NMR (400 MHz, d6-DMSO) δ 9.94 (s, 1H), 8.81 (s, 1H), 7.94 (s, 1H), 7.43 (s, 1H), 7.40 (dd, J=8, 2 Hz, 1H), 7.30 (d, J=2 Hz, 1H), 7.22 (d, J=8 Hz, 1H), 4.68 (d, J=6 Hz, 1H), 3.65 (s, 3H), 3.45 (s, 3H), 2.61 (s, 3H), 2.07 (s, 3H), 1.49 (d, J=6 Hz, 3H). MS m/z 406.4 (M+1).

Workup

  1. temperaturewas heated at 100° C. for 3 h
  2. temperatureSubsequently, the reaction was cooled to rt
  3. custompartitioned with EtOAc (30 mL) and 5% aq NaHCO3 (20 mL)
  4. extractionThe aqueous layer was extracted with fresh EtOAc (2×20 mL)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. customThe crude material was purified by flash column chromatography on silica with DCM/2% MeOH as eluant

Sources & evidence

ORD record
ord-d8e82f75327d4e898e8972366f9ed04f
Source dataset
uspto-grants-2012_10
Patent number
US08278452B2

Reaction notes

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