Diethylcarbamoyl chloride → Diethyl-carbamic acid 5-diethylcarbamoyloxy-2-isopropyl-4-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carbonyl]-cyclohexa-1,3-dienyl ester

HRID 1182812Notes

Reaction equation

HRID 1182812 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([CH:9]([CH3:11])[CH3:10])=[CH:4][C:3]=1[C:12]([N:14]1[CH2:22][C:21]2[C:16](=[CH:17][CH:18]=[C:19]([CH2:23][N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)[CH:20]=2)[CH2:15]1)=[O:13].C[CH2:32][N:33]([CH2:36][CH3:37])[CH2:34][CH3:35].[CH2:38]([N:40]([CH2:44][CH3:45])[C:41](Cl)=[O:42])[CH3:39].C([O-])([O-])=[O:47].[K+].[K+]>C1COCC1.CCOC(C)=O>[CH2:34]([N:33]([CH2:36][CH3:37])[C:32]([O:1][CH:2]1[CH2:7][C:6]([O:8][C:41](=[O:42])[N:40]([CH2:44][CH3:45])[CH2:38][CH3:39])=[C:5]([CH:9]([CH3:10])[CH3:11])[CH:4]=[C:3]1[C:12]([N:14]1[CH2:22][C:21]2[C:16](=[CH:17][CH:18]=[C:19]([CH2:23][N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)[CH:20]=2)[CH2:15]1)=[O:13])=[O:47])[CH3:35]

Participants

7

Reactant 4

HCID 6916Diethylcarbamoyl chlorideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 11955716Onalespib

Product 1

HCID 67104276Diethyl-carbamic acid 5-diethylcarbamoyloxy-2-isopropyl-4-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carbonyl]-cyclohexa-1,3-dienyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2,4-dihydroxy-5-isopropyl-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl]-methanone (1.0 g, 2.44 mmol) in THF (25 mL) containing Et3N (0.68 mL, 4.88 mmol) and N,N-4-dimethylaminopyridine (5 mg, 0.41 mmol) was added N,N-diethylcarbamoyl chloride (1.5 mL, 11.62 mmol). The solution was heated to 60° C. for 18 h when EtOAc (50 mL) and 10% aq K2CO3 (50 mL) were added. The organic phase was washed with saturated brine (30 mL) and the organic phase was separated and evaporated to a small volume. A solution of the residue in DCM was applied to a column containing silica gel and the product eluted successively with DCM followed by 0.2% aqueous ammonia in 5% MeOH in DCM. The fractions containing product were evaporated from DCM followed by diethyl ether to give the title compound as a foam 1.07 g. 1H NMR (400 MHz, DMSO-d6): 7.44 (1H, d), 7.37-7.30 (1H, m), 7.30-7.15 (2H, m), 7.01 (1H, s), 4.75 (2H, s), 4.61 (2H, d), 3.56-3.40 (4H, m), 3.33 (4H, d), 3.24 (3H, d), 3.19-3.09 (2H, m), 3.09-2.95 (2H, m), 2.85-2.56 (4H, m), 2.42 (3H, s), 1.38-0.76 (18H, m); m/z 608 (MH).

Workup

  1. additionwere added
  2. washThe organic phase was washed with saturated brine (30 mL)
  3. customthe organic phase was separated
  4. customevaporated to a small volume
  5. additioncontaining silica gel
  6. washthe product eluted successively with DCM
  7. additionThe fractions containing product
  8. customwere evaporated from DCM

Sources & evidence

ORD record
ord-32ba5cc58e084eb89fa04b2547fa7a30
Source dataset
uspto-grants-2014_03
Patent number
US08664218B2

Reaction notes

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