Dimethylformamide → Bms-066

HRID 17103

Reaction equation

HRID 17103 reaction equation
Cl.[CH3:2][N:3]([CH3:12])[CH2:4][CH2:5][CH2:6][N:7]=[C:8]=[N:9][CH2:10]C.O[N:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=N1.C([N:26]([CH:29](C)C)CC)(C)C.[CH3:32][O:33][CH2:34][C:35]([OH:37])=O.[C:38](O)([C:40](F)(F)F)=O.C[N:46](C)C=O>O.CO>[CH3:2][N:3]1[C:4]2=[C:38]3[CH:40]=[C:10]([C:18]4[N:14]=[C:22]([CH2:17][NH:16][C:35](=[O:37])[CH2:34][O:33][CH3:32])[CH:21]=[CH:20][CH:19]=4)[NH:9][C:8]3=[N:7][C:6]([NH:26][CH3:29])=[C:5]2[N:46]=[CH:12]1

Participants

9

Reactant 6

HCID 6228DimethylformamideHCID 6422Trifluoroacetic acid2×HCID 12251Methoxyacetic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 24825710Bms-066

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

To a mixture of A215.1-trihydrochloride (1.15 g, 2.76 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.794 g, 4.14 mmol), 1-hydroxybenzotriazole (0.559 g, 4.14 mmol), and diisopropylethylamine (2.90 mL, 16.6 mmol) in anhydrous dimethylformamide (50 mL) was added methoxyacetic acid (0.320 mL, 4.14 mmol). The reaction mixture was stirred at 80° C. for 20 min. During the first 5 min, the suspension became homogeneous. The solvent was removed under reduced pressure, and the residue was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. Concentration under pressure followed by purification by flash silica gel chromatography using a mixture of methanol in dichloromethane (2%-5%) afforded 0.890 g (85%) of A228 as yellowish-brown solid. The solid was triturated with methanol to give 0.660 g of A228 as a yellow solid. The filtrate was re-purified on silica gel to give an additional 0.191 g of A228. The compound had an HPLC retention time=1.81 min. (Column: Chromolith SpeedROD 4.6×50 mm—4 min.; Solvent A=10% MeOH, 90% H2O, and 0.1% TFA; Solvent B=90% MeOH, 10% H2O, and 0.1% TFA) and a LC/MS M+1=380.33.

Workup

  1. additionTo a mixture of A215
  2. customDuring the first 5 min
  3. customThe solvent was removed under reduced pressure
  4. additionthe residue was diluted with dichloromethane
  5. washwashed with a saturated aqueous solution of sodium bicarbonate
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationConcentration under pressure
  8. customfollowed by purification by flash silica gel chromatography
  9. additiona mixture of methanol in dichloromethane (2%-5%)
  10. customafforded 0.890 g (85%) of A228 as yellowish-brown solid
  11. customThe solid was triturated with methanol
  12. customto give 0.660 g of A228 as a yellow solid
  13. customThe filtrate was re-purified on silica gel
  14. customto give an additional 0.191 g of A228

Sources & evidence

ORD record
ord-63b762c955fe4f098af02c47678316af
Source dataset
uspto-grants-2010_06
Patent number
US07737279B2

Linked notes

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