Methyl chloroformate → HCID 57925939, compound

HRID 1013509Notes

Reaction equation

HRID 1013509 reaction equation
[CH3:1][P:2]([CH2:5][CH2:6][NH:7][CH2:8][C:9]1[CH:37]=[CH:36][C:12]([C:13]([NH:15][C:16]2[CH:17]=[C:18]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:19]=[CH:20][C:21]=2[NH:22]C(=O)OC(C)(C)C)=[O:14])=[CH:11][CH:10]=1)([CH3:4])=[O:3].CCN(C(C)C)C(C)C.Cl[C:48]([O:50][CH3:51])=[O:49]>C(Cl)Cl.C(O)(C(F)(F)F)=O.ClCCCl>[NH2:22][C:21]1[CH:20]=[CH:19][C:18]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[CH:17][C:16]=1[NH:15][C:13]([C:12]1[CH:11]=[CH:10][C:9]([CH2:8][N:7]([CH2:6][CH2:5][P:2]([CH3:1])([CH3:4])=[O:3])[C:48](=[O:49])[O:50][CH3:51])=[CH:37][CH:36]=1)=[O:14]

Participants

7

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 57925845HCID 57925845, compound

Product 1

HCID 57925939HCID 57925939, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent3×HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of tert-butyl (3-{[4-({[2-(dimethylphosphoryl)ethyl]amino}methyl)benzoyl]amino}biphenyl-4-yl)carbamate (295 mg, 0.566 mmol) in CH2Cl2 (10 mL) were added DIEA (198 μl, 1.13 mmol) and methyl chloroformate (70 mg, 0.735 mmol). After stirring for 30 min at room temperature, the reaction was diluted with CH2Cl2 and washed with saturated NaHCO3. The aqueous layer was extracted with additional CH2Cl2. The combined organic layers were washed with brine, dried (MgSO4), and evaporated. Flash chromatography (0-10% MeOH/CH2Cl2) afforded a colorless solid. This solid was taken up in CH2Cl2 (5 mL) and TFA (1 mL). After stirring at room temperature for 1 h, the solution was diluted with 1,2-DCE and concentrated. The residue was diluted with EtOAc, washed with saturated NaHCO3 and brine, dried (MgSO4), and evaporated to afford the title compound as a pale yellow solid. NMR (DMSO-d6, 600 MHz) δ 9.70 (bs, 1H), 7.96 (d, J=8.1 Hz, 2H), 7.54-7.50 (m, 2H), 7.50-7.48 (m, 1H), 7.37-7.32 (m, 4H), 7.29 (dd, J=8.2, 2.1 Hz, 1H), 7.20 (t, J=7.4 Hz, 1H), 6.83 (d, J=8.5 Hz, 1H), 5.07 (bs, 2H), 4.52 (s, 2H), 3.69-3.57 (m, 3H), 3.45-3.34 (m, 2H), 1.99-1.87 (m, 2H), 1.34 (d, J=12.9 Hz, 6H). MS: cal'd 480 (MH+), exp 480 (MH+).

Workup

  1. washwashed with saturated NaHCO3
  2. extractionThe aqueous layer was extracted with additional CH2Cl2
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customFlash chromatography (0-10% MeOH/CH2Cl2) afforded a colorless solid
  7. stirringAfter stirring at room temperature for 1 h
  8. concentrationconcentrated
  9. additionThe residue was diluted with EtOAc
  10. washwashed with saturated NaHCO3 and brine
  11. dry with materialdried (MgSO4)
  12. customevaporated

Sources & evidence

ORD record
ord-7ccb1ead21944b5093580683dd975b22
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

Loading…