Methyl chloroformate → HCID 59313746, compound

HRID 889459Notes

Reaction equation

HRID 889459 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:11]=[C:12]([N:21]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[C:13]3[N:14]([C:16]([C:19]#[N:20])=[CH:17][N:18]=3)[N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].CCN(C(C)C)C(C)C.Cl[C:47]([O:49][CH3:50])=[O:48]>C1COCC1>[C:19]([C:16]1[N:14]2[N:15]=[C:10]([NH:9][C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([NH:1][C:47](=[O:48])[O:49][CH3:50])[CH:3]=3)[CH:11]=[C:12]([N:21]([CH2:28][C:29]3[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[C:13]2=[N:18][CH:17]=1)#[N:20]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 59313889HCID 59313889, compound

Product 1

HCID 59313746HCID 59313746, compoundYield 16.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 8B (82 mg, 0.17 mmol) in THF (3 mL) was treated with DIEA (0.039 mL, 0.22 mmol), followed by methyl chloroformate (0.048 mL, 0.62 mmol). The resulting solution was stirred at room temperature for 12 hours and then concentrated to dryness. The crude product was dissolved in a small amount of DCM and purified by flash chromatography (SiO2, DCM to 20% ethyl acetate/DCM, 24 g column, 40 min. gradient) to afford 8C (15 mg, 16.3%). HPLC: Rt=3.98 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min. gradient, monitored at 220 nm). MS (ES): m/z=539.2 [M+H]+.

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe crude product was dissolved in a small amount of DCM
  3. custompurified by flash chromatography (SiO2, DCM to 20% ethyl acetate/DCM, 24 g column, 40 min. gradient)

Sources & evidence

ORD record
ord-81ec8822e4d640b1ad07fd48ad4edd1e
Source dataset
uspto-grants-2012_08
Patent number
US08252795B2

Reaction notes

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