Triethylamine → (2R,4R)-9-(2-morpholin-4-ylethyl)-N-(2-phenylpropan-2-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxamide

HRID 1623893Notes

Reaction equation

HRID 1623893 reaction equation
[CH2:1]1[C@@H:3]2[CH2:4][C:5]3[C:6]([C:10]([OH:12])=O)=[N:7][NH:8][C:9]=3[C@H:2]12.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[C:44]1([C:50]([NH2:53])([CH3:52])[CH3:51])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.Cl.Cl[CH2:56][CH2:57][N:58]1[CH2:63][CH2:62][O:61][CH2:60][CH2:59]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:51][C:50]([NH:53][C:10]([C:6]1[C:5]2[CH2:4][C@H:3]3[CH2:1][C@H:2]3[C:9]=2[N:8]([CH2:56][CH2:57][N:58]2[CH2:63][CH2:62][O:61][CH2:60][CH2:59]2)[N:7]=1)=[O:12])([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[CH3:52]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 68509CumylamineHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 49763030MK-1903

Product 1

HCID 86669645(2R,4R)-9-(2-morpholin-4-ylethyl)-N-(2-phenylpropan-2-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxamideYield 12.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (1aR,5aR)-1a,2,5,5a-tetrahydro-1H-2,3-diazacyclopropa[a]pentalene-4-carboxylic acid (40 mg, 0.24 mmol), HATU (93 mg, 0.24 mmol) in DMF (1 mL) was added Et3N (25 mg, 0.24 mmol). After stirring for 5 min at room temperature, 2-phenylpropan-2-amine (33 mg, 0.24 mmol) was added to the reaction. After stirring for an additional 1 h, 4-(2-chloroethyl)morpholine hydrochloride (45 mg, 0.24 mmol) and Cs2CO3 (79 mg, 0.24 mmol) was added into the reaction. The reaction was microwaved for 3.5 h at 150° C., filtered, and purified by preparative HPLC to give the title compound (12 mg). LCMS m/z=395.5 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 0.38 (td, J=4.6 and 3.5 Hz, 1H), 1.10 (td, J=7.8 and 4.7 Hz, 1H), 1.78 (s, 6H), 2.00-2.06 (m, 1H), 2.16-2.23 (m, 1H), 2.48-2.52 (m, 4H), 2.76-2.94 (m, 4H), 3.67-3.72 (m, 4H), 4.17 (t, J=6.8 Hz, 2H), 7.07 (bs, 1H), 7.21 (t, J=8.0 Hz, 1H), 7.32 (t, J=8.0 Hz, 2H), 7.42-7.47 (m, 2H).

Workup

  1. stirringAfter stirring for an additional 1 h
  2. customThe reaction was microwaved for 3.5 h at 150° C.
  3. filtrationfiltered
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-5b7fa92f140e48b286dc182d712c7ed8
Source dataset
uspto-grants-2014_07
Patent number
US08778950B2

Reaction notes

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