4-Methylmorpholine → HCID 86670547, compound

HRID 874710Notes

Reaction equation

HRID 874710 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][Si:13]([CH3:16])([CH3:15])[CH3:14])=[CH:7][C:3]=1[C:4](O)=[O:5].CN([C:20]([O:24][N:25]1N=NC2C=CC=C[C:26]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.Cl.CNOC>O.CN(C=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][Si:13]([CH3:16])([CH3:15])[CH3:14])=[CH:7][C:3]=1[C:4]([N:25]([O:24][CH3:20])[CH3:26])=[O:5]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67167639HCID 67167639, compound

Product 1

HCID 86670547HCID 86670547, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-amino-5-[2-(trimethylsilyl)ethynyl]benzoic acid (630 mg, 2.7 mmol, 1 eq.), HBTU (1.54 g, 4.0 mmol, 1.5 eq.), and 4-methylmorpholine (0.74 mL, 6.7 mmol, 2.5 eq.) were added, in order, to DMF (10 mL) and stirred at room temperature for 10 minutes. N,O-dimethylhydroxylamine hydrochloride (290 mg, 3.0 mmol, 1.1 eq.) was then added to the reaction, and the reaction was stirred at room temperature for 16 hours. Water was then added (20 mL), and the reaction was extracted three times with ethyl acetate (50 mL each). To remove residual water, saturated sodium chloride (20 mL) was added to the organic layer, and the organic layer was separated and dried over sodium sulfate. The solvent was evaporated by rotary evaporation, and the residue was purified on silica column (hexanes/ethyl acetate, 3:1) to result in 320 mg (43%) of the title compound as an orange solid. 1H NMR (500 MHz, CDCl3) δ 8.38 (d, J=1.5, 1H, Ar—H), 7.82 (dd, J=1.5, 7.5, 1H, AR—H), 7.10 (d, J=7.3, 1H, Ar—H), 5.61 (s, 2H, NH2), 4.09 (s, 3H, OCH3), 3.66 (s, 3H, NCH3), 0.22 (s, 9H, Si(CH3)3). 13C NMR (126 MHz, CDCl3) δ 169.20 (CON), 147.35 (C—Ar), 135.24 (C—Ar), 133.50 (C—Ar), 116.65 (C—Ar), 116.55 (C—Ar), 111.21 (C—Ar), 105.40 (CSi(CH3)3), 91.90 (CCSi(CH3)3), 61.44 (NOCH3), 34.53 (NCH3), 0.29 (Si(CH3)3). Exact Mass, 276.13. 277.1046 [M+H]+.

Workup

  1. stirringthe reaction was stirred at room temperature for 16 hours
  2. extractionthe reaction was extracted three times with ethyl acetate (50 mL each)
  3. customTo remove residual water, saturated sodium chloride (20 mL)
  4. additionwas added to the organic layer
  5. customthe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was evaporated by rotary evaporation
  8. customthe residue was purified on silica column (hexanes/ethyl acetate, 3:1)

Sources & evidence

ORD record
ord-9a66cf01d215405b818537ac4bb87a81
Source dataset
uspto-grants-2015_03
Patent number
US08980926B2

Reaction notes

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