Trimethyl orthoformate → HCID 58266341, compound

HRID 1888600Notes

Reaction equation

HRID 1888600 reaction equation
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:30]=[N:29][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([C:25]([NH:27][NH2:28])=[O:26])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:31]OC(OC)OC.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(O)(=O)C>[O:26]1[CH:31]=[N:28][N:27]=[C:25]1[C:22]1[N:23]=[CH:24][C:19]2[NH:18][C:17]3[N:29]=[CH:30][C:14]([C:11]4[CH:12]=[CH:13][C:8]([CH2:7][N:1]5[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]5)=[CH:9][CH:10]=4)=[CH:15][C:16]=3[C:20]=2[CH:21]=1

Participants

6

Reactant 3

HCID 9005Trimethyl orthoformate2×HCID 516892Sodium BicarbonateHCID 58266826HCID 58266826, compound

Product 1

HCID 58266341HCID 58266341, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbhydrazide (53.8 mg, 0.134 mmol) and trimethoxymethane (1.21 mL, 11.0 mmol) in DMF (0.81 mL) was heated at 120° C. for 24 h. The mixture was cooled, treated with trimethoxymethane (1.0 mL) and a few drops of acetic acid and heated under reflux for 48 h. The mixture was allowed to cool, treated with saturated aqueous sodium bicarbonate solution, and the resultant white precipitate collected by filtration and washed with water. The filtrate was extracted with DCM, 20% methanol in DCM, and the combined organic phases dried over sodium sulfate, combined with the isolated solid and concentrated in vacuo. The resultant residue was purified by preparative HPLC [2-60% MeCN/water modified with 0.1% ammonium hydroxide] to afford a light-yellow flaky solid (6.0 mg, 27%). 1H NMR (DMSO-D6, 400 MHz): 12.77-12.69 (s, 1H), 9.41 (s, 1H), 9.26 (d, J=2.2 Hz, 1H), 9.18 (s, 1H), 9.08 (s, 1H), 9.00 (d, J=2.2 Hz, 1H), 8.31 (s, 1H), 7.80 (d, J=8.1 Hz, 2H), 7.46 (d, J=8.1 Hz, 2H), 3.50 (s, 2H), 2.37 (m, 4H), 1.52 (m, 4H), 1.41 (m, 2H). LCMS (Method D): RT=7.69 min, M+H+=411.

Workup

  1. temperatureThe mixture was cooled
  2. temperatureheated
  3. temperatureunder reflux for 48 h
  4. temperatureto cool
  5. filtrationthe resultant white precipitate collected by filtration
  6. washwashed with water
  7. extractionThe filtrate was extracted with DCM, 20% methanol in DCM
  8. dry with materialthe combined organic phases dried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe resultant residue was purified by preparative HPLC [2-60% MeCN/water modified with 0.1% ammonium hydroxide]

Sources & evidence

ORD record
ord-5e2c08d78ce245c8ac2cd22d5d8038f7
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

Loading…