Methyl chloroformate → HCID 58236616, compound

HRID 409974Notes

Reaction equation

HRID 409974 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:30][NH:31][CH2:32][CH2:33][O:34][CH3:35])=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:36])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.Cl[C:38]([O:40][CH3:41])=[O:39].CCN(C(C)C)C(C)C>C1COCC1>[CH3:41][O:40][C:38](=[O:39])[N:31]([CH2:30][C:27]1[CH:26]=[N:25][C:24]([C:22]2[S:23][C:16]3[C:17](=[N:18][CH:19]=[CH:20][C:15]=3[O:14][C:11]3[CH:12]=[CH:13][C:8]([NH:7][C:5]([NH:4][CH:1]4[CH2:3][CH2:2]4)=[O:6])=[CH:9][C:10]=3[F:36])[CH:21]=2)=[CH:29][CH:28]=1)[CH2:32][CH2:33][O:34][CH3:35]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 44229901HCID 44229901, compound

Product 1

HCID 58236616HCID 58236616, compoundYield 50.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound 339 (220 mg, 0.433 mmol) and methyl chloroformate (50.2 μl, 0.65 mmol) in THF (4 ml) was added DIPEA (227 μl, 1.30 mmol) and the mixture was stirred at room temperature for 18 h. The solvent was removed under reduced pressure, the residue was triturated with MeOH and the solid suspension was collected by filtration and purified via Biotage (linear gradient 0-20%, methanol/dichloromethane; Snap 25 g column) to afford compound 340 (123.1 mg, 0.218 mmol, 50.2% yield) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.70 (s, 1H), 8.56-8.50 (m, 2H), 8.33 (s, 1H), 8.25 (d, J=8.0 Hz, 1H), 7.84-7.77 (m, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.2 Hz, 1H), 7.20 (dd, J=8.8, 1.2 Hz, 1H), 6.65 (d, J=5.6 Hz, 1H), 6.56 (d, J=2.8 Hz, 1H), 4.54 (s, 2H), 3.64 (s, 2H), 3.44 (s, 3H), 3.22 (s, 2H), 2.59-2.51 (m, 1H), 0.69-0.62 (m, 2H), 0.46-0.40 (m, 2H). MS (m/z): 566.1 (M+H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was triturated with MeOH
  3. filtrationthe solid suspension was collected by filtration
  4. custompurified via Biotage (linear gradient 0-20%, methanol/dichloromethane; Snap 25 g column)

Sources & evidence

ORD record
ord-9f1ecaab0b9c4b549ad0ed882cbfddf1
Source dataset
uspto-grants-2014_06
Patent number
US08759522B2

Reaction notes

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