Diisopropylethylamine → HCID 68576486, compound

HRID 272982Notes

Reaction equation

HRID 272982 reaction equation
[CH3:1][O:2][CH2:3][C:4](Cl)=[O:5].[N:7]1([CH2:12][CH2:13][CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3([C:28]([N:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)=[O:29])[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:18][CH:17]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1.C(N(CC)C(C)C)(C)C>ClCCl>[CH3:1][O:2][CH2:3][C:4]([N:33]1[CH2:34][CH2:35][N:30]([C:28]([C:22]2([C:19]3[CH:20]=[CH:21][C:16]([O:15][CH2:14][CH2:13][CH2:12][N:7]4[CH2:8][CH2:9][CH2:10][CH2:11]4)=[CH:17][CH:18]=3)[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)=[O:29])[CH2:31][CH2:32]1)=[O:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 68576545HCID 68576545, compound

Product 1

HCID 68576486HCID 68576486, compoundYield 67.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Methoxyacetyl chloride (55 μl, 0.6 mmol) was added dropwise at 0° C. to a solution of 1-({4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}carbonyl)piperazine of example 181 (200 mg, 0.5 mmol) and N,N-diisopropylethylamine (100 μl, 0.6 mmol) in dichloromethane (3 ml). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane (20 ml) and washed with 2N sodium hydroxide (20 ml). The layers were separated and the aqueous layer was further extracted with dichloromethane (20 ml). The organics were combined, dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (97:3:0.3 to 90:10:1 by volume) to provide the title compound (160 mg, 67%). HRMS ESI+ m/z 474.2952 [MH]+.

Workup

  1. washwashed with 2N sodium hydroxide (20 ml)
  2. customThe layers were separated
  3. extractionthe aqueous layer was further extracted with dichloromethane (20 ml)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (97:3:0.3 to 90:10:1 by volume)

Sources & evidence

ORD record
ord-8187207397c2491d8326da3354972e05
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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