3-Hydroxy-2,2-dimethylpropionic acid → HCID 44200546, compound

HRID 2061167Notes

Reaction equation

HRID 2061167 reaction equation
[OH:1][CH2:2][C:3]([CH3:8])([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.[CH3:42][N:43]1[C:52]2[C:47](=[CH:48][N:49]=[C:50]([CH3:53])[CH:51]=2)[CH:46]=[C:45]([C:54]2[CH:55]=[C:56]([NH:61]/[C:62](/[NH2:65])=[N:63]/O)[CH:57]=[CH:58][C:59]=2[CH3:60])[C:44]1=[O:66]>CN(C=O)C>[OH:1][CH2:2][C:3]([C:4]1[O:6][N:63]=[C:62]([NH:61][C:56]2[CH:57]=[CH:58][C:59]([CH3:60])=[C:54]([C:45]3[C:44](=[O:66])[N:43]([CH3:42])[C:52]4[C:47]([CH:46]=3)=[CH:48][N:49]=[C:50]([CH3:53])[CH:51]=4)[CH:55]=2)[N:65]=1)([CH3:8])[CH3:7]

Participants

6

Reactant 4

HCID 785483-Hydroxy-2,2-dimethylpropionic acidHCID 81531DiisopropylethylamineHCID 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 44200546HCID 44200546, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-hydroxy-2,2-dimethylpropanoic acid (88 mg, 0.7 mmol) in DMF (5 mL) were added DIPEA (0.26 mL, 1.5 mmol) and HATU (0.21 g, 0.7 mmol). After stirring at rt for 15 min, 17 (0.25 g, 0.7 mmol) was added as a solution in DMF (2 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 2 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/4% MeOH as eluant to give 3-(5-(5-(1-hydroxy-2-methylpropan-2-yl)-1,2,4-oxadiazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one (A35) as a clear glassy solid. 1H NMR (400 MHz, d6-DMSO) 9.86 (s, 1H), 8.81 (s, 1H), 7.93 (s, 1H), 7.43 (s, 1H), 7.37 (dd, J=8, 2 Hz, 1H), 7.28 (d, J=2 Hz, 1H), 7.21 (d, J=8 Hz, 2H), 5.10 (t, J=5.5 Hz, 1H), 3.65 (s, 3H), 3.55, (d, J=5.5 Hz, 1H) 2.61 (s, 3H), 2.07 (s, 3H), 1.31 (s, 6H). MS m/z 420.4 (M+1).

Workup

  1. temperaturewas heated at 100° C. for 2 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/4% MeOH as eluant

Sources & evidence

ORD record
ord-243aed57ae684c3db948a3de348b9d36
Source dataset
uspto-grants-2012_10
Patent number
US08278452B2

Reaction notes

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