Diisopropylethylamine → HCID 46908501, compound

HRID 1694322Notes

Reaction equation

HRID 1694322 reaction equation
[S:1]([N:11]1[CH2:16][CH2:15][N:14]2[CH:17]=[CH:18][CH:19]=[C:13]2[CH:12]1[CH2:20][C:21]([OH:23])=O)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:57][C@@H:58]([C:60]1[CH:71]=[CH:70][C:63]([CH2:64][NH:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[CH:62][CH:61]=1)[CH3:59]>C1COCC1.C(Cl)Cl>[C:66]([NH:65][CH2:64][C:63]1[CH:62]=[CH:61][C:60]([C@H:58]([NH:57][C:21](=[O:23])[CH2:20][CH:12]2[N:11]([S:1]([C:4]3[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=3)(=[O:3])=[O:2])[CH2:16][CH2:15][N:14]3[CH:17]=[CH:18][CH:19]=[C:13]23)[CH3:59])=[CH:71][CH:70]=1)([CH3:69])([CH3:67])[CH3:68]

Participants

7

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 59486400HCID 59486400, compoundHCID 59486435HCID 59486435, compound

Product 1

HCID 46908501HCID 46908501, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 2-(2-tosyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-1-yl)acetic acid (S11) (405 mg, 1.2 mmol, 1.0 eq.) in THF (5 ml) were added DIPEA (1.0 ml, 6.0 mmol, 5.0 eq.) and HATU (547 mg, 1.4 mmol, 1.2 eq.) at 0° C. and the mixture was stirred for 15 min at the same temperature. A solution of (R)—N-(4-(1-aminoethyl)-benzyl)-2-methylpropan-2-amine (A54) (1.2 mmol, 1.0 eq.) in THF (3 ml) was added to the reaction mixture and it was stirred at RT for 16 h. The mixture was diluted with DCM (70 ml) and washed with sat. NH4Cl solution (25 ml), sat. NaHCO3 solution (25 ml), water (25 ml) and brine (25 ml). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give the crude product which was purified by column chromatography (silica gel; 3% MeOH/DCM) to yield the desired product as a light brown solid. Yield: 29% (180 mg, 0.334 mmol); MS, Rt=2.9 min; m/z=523.1 [M H]+

Workup

  1. stirringwas stirred at RT for 16 h
  2. washwashed with sat. NH4Cl solution (25 ml), sat. NaHCO3 solution (25 ml), water (25 ml) and brine (25 ml)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto give the crude product which
  6. customwas purified by column chromatography (silica gel; 3% MeOH/DCM)

Sources & evidence

ORD record
ord-c7ce50516892478bb2538c9642d01f09
Source dataset
uspto-grants-2012_04
Patent number
US08158628B2

Reaction notes

Loading…