Diisopropylethylamine → 3-{6-[4-(2-Diisopropylaminoethylamino)benzenesulfonyloxy]benzothiazol-2-yl-carbamoyl}azetidine-1-carboxylic acid tert-butyl ester

HRID 1867977Notes

Reaction equation

HRID 1867977 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:48][C:49]1[S:50][C:51]2[CH:57]=[C:56]([O:58][S:59]([C:62]3[CH:67]=[CH:66][C:65]([NH:68][CH2:69][CH2:70][N:71]([CH:75]([CH3:77])[CH3:76])[CH:72]([CH3:74])[CH3:73])=[CH:64][CH:63]=3)(=[O:61])=[O:60])[CH:55]=[CH:54][C:52]=2[N:53]=1>CN(C)C=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([C:12](=[O:14])[NH:48][C:49]2[S:50][C:51]3[CH:57]=[C:56]([O:58][S:59]([C:62]4[CH:67]=[CH:66][C:65]([NH:68][CH2:69][CH2:70][N:71]([CH:75]([CH3:77])[CH3:76])[CH:72]([CH3:73])[CH3:74])=[CH:64][CH:63]=4)(=[O:61])=[O:60])[CH:55]=[CH:54][C:52]=3[N:53]=2)[CH2:11]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 579808584-(2-Diisopropylaminoethylamino)benzenesulfonic acid 2-aminobenzothiazol-6-yl ester

Product 1

HCID 579808573-{6-[4-(2-Diisopropylaminoethylamino)benzenesulfonyloxy]benzothiazol-2-yl-carbamoyl}azetidine-1-carboxylic acid tert-butyl esterYield 27.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

68 mg of azetidine-1,3-dicarboxylic acid mono-tert-butyl ester, 256 mg of HBTU and 235 μl of DIEA are added to a solution of 4-(2-diisopropylamino-ethylamino)benzenesulfonic acid 2-aminobenzothiazol-6-yl ester (inter-mediate 34) (100 mg, 0.225 mmol) in 5 ml of dimethylformamide. The solution obtained is stirred for 20 hours at room temperature. After addition of 50 ml of water, the reaction medium is extracted with 3 times 25 ml of ethyl acetate. The extracts are dried over magnesium sulfate, filtered and evaporated under reduced pressure to give 700 mg of crude oil. This oil is purified by elution in a 95/5 dichloromethane/methanol mixture at a flow rate of 10 ml/minute, on 20 g of silica, to give 39 mg of 3-{6-[4-(2-diisopropylaminoethylamino)-benzenesulfonyloxy]benzothiazol-2-ylcarbamoyl}azetidine-1-carboxylic acid tert-butyl ester.

Workup

  1. customThe solution obtained
  2. extractionthe reaction medium is extracted with 3 times 25 ml of ethyl acetate
  3. dry with materialThe extracts are dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customto give 700 mg of crude oil
  7. customThis oil is purified by elution in a 95/5 dichloromethane/methanol mixture at a flow rate of 10 ml/minute, on 20 g of silica

Sources & evidence

ORD record
ord-1276d23cd1814d6c8da2a8fbbefab2d8
Source dataset
uspto-grants-2009_12
Patent number
US07632952B2

Reaction notes

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