Diisopropylethylamine → 1-(4-Cyclopropylbuta-1,3-diyn-1-yl)-4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}benzene

HRID 1519680Notes

Reaction equation

HRID 1519680 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH:34]1([C:37]#[C:38][C:39]#[C:40][C:41]2[CH:49]=[CH:48][C:44]([C:45]([OH:47])=O)=[CH:43][CH:42]=2)[CH2:36][CH2:35]1.Cl.[CH3:51][NH:52][C:53](=[O:61])[C@H:54]([C:57](=[O:60])[O:58][CH3:59])[NH:55][CH3:56]>O.C(OCC)(=O)C.CN(C=O)C>[CH:34]1([C:37]#[C:38][C:39]#[C:40][C:41]2[CH:42]=[CH:43][C:44]([C:45](=[O:47])[N:55]([CH:54]([C:53]([NH:52][CH3:51])=[O:61])[C:57]([O:58][CH3:59])=[O:60])[CH3:56])=[CH:48][CH:49]=2)[CH2:35][CH2:36]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594169284-(4-Cyclopropylbuta-1,3-diyn-1-yl)benzoic acidHCID 86679246N,N2,O-trimethyl-3-oxoserinamide hydrochloride2×

Product 1

HCID 866792591-(4-Cyclopropylbuta-1,3-diyn-1-yl)-4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}benzeneYield 115.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (1.1 g) and DIPEA (1.0 mL) were added to a DMF (4.0 mL) solution of 4-(4-cyclopropylbuta-1,3-diyn-1-yl)benzoic acid (0.42 g) as obtained in Example 6-(2), whereafter the mixture was stirred for 2.5 hours at room temperature. Then, N,N2,O-trimethyl-3-oxoserinamide hydrochloride (Intermediate 5-2, 0.59 g) was added, and the mixture was stirred for 40 minutes at 70 to 80° C. The reaction mixture was cooled to room temperature, and ethyl acetate and water were added to isolate the organic layer. The extract was washed sequentially with water and brine, and dried over anhydrous magnesium sulfate. The desiccant was filtered out, and then the solvent was distilled off under reduced pressure to obtain 1-(4-cyclopropylbuta-1,3-diyn-1-yl)-4-{[1-methoxy-3-(methylamino)-1,3-dioxopropan-2-yl](methyl)carbamoyl}benzene (brown oil) (0.81 g).

Workup

  1. customas obtained in Example 6-(2), whereafter the mixture
  2. stirringthe mixture was stirred for 40 minutes at 70 to 80° C
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customto isolate the organic layer
  5. washThe extract was washed sequentially with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationThe desiccant was filtered out
  8. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-de2c91356b3b4cca878481dffa795c0b
Source dataset
uspto-grants-2015_07
Patent number
US09073821B2

Reaction notes

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