Acetic Acid → HCID 11704483, compound

HRID 2102375Notes

Reaction equation

HRID 2102375 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]([NH:14][CH3:15])=[O:13])=[N:10][CH:11]=1.[H-].[Na+].Cl[C:19]1[C:20]2[C:27]([C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)=[CH:26][S:25][C:21]=2[N:22]=[CH:23][N:24]=1.C(O)(=O)C>CN(C)C(=O)C>[CH3:15][NH:14][C:12]([C:9]1[CH:8]=[CH:7][C:6]([O:5][CH2:4][CH2:3][CH2:2][O:1][C:19]2[C:20]3[C:27]([C:28]4[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=4)=[CH:26][S:25][C:21]=3[N:22]=[CH:23][N:24]=2)=[CH:11][N:10]=1)=[O:13]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 57803016HCID 57803016, compoundHCID 86616297HCID 86616297, compound

Product 1

HCID 11704483HCID 11704483, compoundYield 683.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

5-(3-Hydroxypropoxy)-N-methylpyridine-2-carboxamide (52 mg, 0.25 mmol) in N,N-dimethylacetamide (2.0 mL, 22 mmol) was treated with sodium hydride (11 mg, 60%, 0.27 mmol) at ambient temperature. After 1.5 hours, the mixture was added to a solution of 4-chloro-5-pyridin-4-ylthieno[2,3-d]pyrimidine (62 mg, 0.025 mmol) in N,N-dimethylacetamide (1.0 mL) and the resulting mixture was stirred at room temperature for 12 hours. The reaction mixture was then quenched by the addition of acetic acid (0.12 mL, 2.0 mmol) and the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (50 mL), washed with 5% aqueous sodium bicarbonate (2×30 mL) and the organic layer was concentrated. The product was purified by silica gel chromatography using 3 to 5% methanol in ethyl acetate to give 72 mg (68%) of N-methyl-5-{3-[(5-pyridin-4-ylthieno[2,3-d]pyrimidin-4-yl)oxy]propoxy}pyridine-2-carboxamide as a white solid. MS [M+H] 422.0, 1H NMR (CDCl3) δ (ppm) 8.74 (s, 1H), 8.66 (s, 1H), 8.54 (d, J=3.9 Hz, 1H), 8.11 (d, J=8.4 Hz, 1H), 8.05 (d, J=2.7 Hz, 1H), 7.90-7.73 (m, 2H), 7.33 (s, 1H), 7.28 (dd, J=7.8, 4.8 Hz, 1H), 7.11 (dd, J=8.7, 2.7 Hz, 1H), 4.62 (t, J=6.0 Hz, 2H), 3.76 (t, J=6.0 Hz, 2H), 3.01 (d, J=4.8 Hz, 3H), 2.13 (t, J=6.0 Hz, 2H).

Workup

  1. customthe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  3. washwashed with 5% aqueous sodium bicarbonate (2×30 mL)
  4. concentrationthe organic layer was concentrated
  5. customThe product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-edda483e61164f11afd9190c67da563a
Source dataset
uspto-grants-2009_08
Patent number
US07576080B2

Reaction notes

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