Diisopropylethylamine → HCID 53329716, compound

HRID 1029033Notes

Reaction equation

HRID 1029033 reaction equation
Cl.[NH2:2][C:3]1[C:12]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:19]3[C:27]([CH2:28][CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=[CH:24][C:20]=3[C:21](O)=[O:22])[CH:9]=2)[N:4]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[F:59][C@@H:60]1[CH2:64][CH2:63][NH:62][CH2:61]1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:2][C:3]1[C:12]([N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:19]3[C:27]([CH2:28][CH2:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[CH:26][CH:25]=[CH:24][C:20]=3[C:21]([N:62]3[CH2:63][CH2:64][C@@H:60]([F:59])[CH2:61]3)=[O:22])[CH:9]=2)[N:4]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71253315HCID 71253315, compound

Product 1

HCID 53329716HCID 53329716, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(2-amino-3-morpholinoquinolin-6-yl)-3-(3,3-dimethylbutyl)benzoic acid hydrochloride (168 mg, 0.357 mmol) and HATU (204 mg, 0.536 mmol) in DMF (5 mL) was stirred for 10 min at RT. (R)-(−)-3-fluoropyrrolidine hydrochloride (224 mg, 1.787 mmol) and 1,1′-dimethyltriethylamine (0.622 mL, 3.57 mmol) were added and the reaction mixture was allowed to stir overnight at RT. The reaction mixture was partitioned between water and ethyl acetate. The organic phase was separated, dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC (10-100% water with 0.1% TFA/CH3CN, 11 min). The obtained product was eluted on an SCX cartridge with MeOH followed by 2M NH3/MeOH. The basic fraction was concentrated to afford the titled compound as a white solid. MS (ESI, pos. ion) m/z: 505 (M+1).

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic phase was separated
  3. dry with materialdried over MgSO4
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was purified by preparative HPLC (10-100% water with 0.1% TFA/CH3CN, 11 min)
  6. washThe obtained product was eluted on an SCX cartridge with MeOH
  7. concentrationThe basic fraction was concentrated

Sources & evidence

ORD record
ord-f3f04fec83ec44d48fea81d6d1593184
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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