Cyclopropanecarbonyl chloride → HCID 86707801, compound

HRID 2174394Notes

Reaction equation

HRID 2174394 reaction equation
[CH:1]1([C:4](Cl)=[O:5])[CH2:3][CH2:2]1.[F:7][C:8]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH2:23][C:22]([C:28]4[CH:33]=[C:32]([Cl:34])[C:31]([Cl:35])=[C:30]([Cl:36])[CH:29]=4)([C:24]([F:27])([F:26])[F:25])[O:21][N:20]=3)=[CH:15][CH:14]=2)[CH2:11][CH:10]([NH2:12])[CH2:9]1.CCN(C(C)C)C(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C>[F:7][C:8]1([C:13]2[CH:14]=[CH:15][C:16]([C:19]3[CH2:23][C:22]([C:28]4[CH:33]=[C:32]([Cl:34])[C:31]([Cl:35])=[C:30]([Cl:36])[CH:29]=4)([C:24]([F:25])([F:26])[F:27])[O:21][N:20]=3)=[CH:17][CH:18]=2)[CH2:11][CH:10]([NH:12][C:4]([CH:1]2[CH2:3][CH2:2]2)=[O:5])[CH2:9]1

Participants

6

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 86707800HCID 86707800, compound

Product 1

HCID 86707801HCID 86707801, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

Cyclopropylcarbonylchloride (14.1 μL, 0.10 mmol) is added to 3-fluoro-3-(4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)cyclobutanamine (Preparation 16, 50.0 mg, 0.10 mmol) in DMF (1.5 mL) along with DIPEA (5.4 μL, 0.31 mmol) and DMAP (1.2 mg, 0.01 mmol). The reaction mixture is stirred for three days at room temperature. The mixture is partitioned between brine (5 mL) and EtOAc (5 mL). The organics are separated, dried over MgSO4, filtered and evaporated to give a residue, which is purified on regular silica eluting from neat DCM to 15% MeOH/DCM to give the title compound (22 mg): 1H NMR (DMSO-d6) δ: 8.83 (1H, d), 7.88 (2H, s), 7.79 (2H, d), 7.58 (2H, d), 4.61-4.53 (1H, m), 4.42-4.30 (2H, m), 2.89-2.78 (2H, m), 2.65-2.55 (2H, m), 1.50-1.44 (1H, m), 0.71-0.61 (4H, m); m/z (Cl) 548.

Workup

  1. customThe mixture is partitioned between brine (5 mL) and EtOAc (5 mL)
  2. customThe organics are separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto give a residue, which
  7. customis purified on regular silica eluting from neat DCM to 15% MeOH/DCM

Sources & evidence

ORD record
ord-b22bb872e38944f7b90447cafbd056b4
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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