Diisopropylethylamine → HCID 49832424, compound

HRID 2038811Notes

Reaction equation

HRID 2038811 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([C:18]([NH:20][C:21]4([C:24]([OH:26])=O)[CH2:23][CH2:22]4)=[O:19])[N:13]3[C@:12]([CH3:39])([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=3)[C:11]2=[O:40])[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8].Cl.[CH3:42][N:43]1[CH:47]=[C:46]([C:48]2[CH:49]=[N:50][C:51]([C:54]3([NH2:57])[CH2:56][CH2:55]3)=[N:52][CH:53]=2)[CH:45]=[N:44]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:42][N:43]1[CH:47]=[C:46]([C:48]2[CH:53]=[N:52][C:51]([C:54]3([NH:57][C:24]([C:21]4([NH:20][C:18]([C:17]5[N:13]6[C@:12]([CH3:39])([CH2:27][C:28]7[CH:33]=[CH:32][C:31]([O:34][C:35]([F:37])([F:36])[F:38])=[CH:30][CH:29]=7)[C:11](=[O:40])[N:10]([C:4]7[CH:5]=[C:6]([Cl:9])[C:7]([F:8])=[C:2]([Cl:1])[CH:3]=7)[C:14]6=[N:15][CH:16]=5)=[O:19])[CH2:23][CH2:22]4)=[O:26])[CH2:56][CH2:55]3)=[N:50][CH:49]=2)[CH:45]=[N:44]1

Participants

6

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 67515473HCID 67515473, compoundHCID 87382236HCID 87382236, compound

Product 1

HCID 49832424HCID 49832424, compoundYield 83.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-{[(R)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid (130 mg, 0.22 mmol) and 1-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-cyclopropylamine hydrochloride (75 mg, 0.26 mmol) in DMF (1 mL) was added diisopropylethylamine (0.15 mL, 0.87 mmol) and HATU (990 mg, 0.24). After 1 h, the reaction mixture was purified by reversed phase MPLC (C18, 30 g, Mobile phase: CH3CN (0.1% TFA), water (0.1% TFA), Gradient: 70% water to 10% water). The pure fractions were combined and concentrated in-vacuo to remove most of the CH3CN and then partitioned between 50 mL of CH2Cl2, 20 mL of water, and 10 mL of saturated aqueous NaHCO3 solution. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated to afford 146 mg of the title compound as a white foam, m/z=798.8.

Workup

  1. customthe reaction mixture was purified by reversed phase MPLC (C18, 30 g, Mobile phase: CH3CN (0.1% TFA), water (0.1% TFA), Gradient: 70% water to 10% water)
  2. concentrationconcentrated in-vacuo
  3. customto remove most of the CH3CN
  4. custompartitioned between 50 mL of CH2Cl2, 20 mL of water, and 10 mL of saturated aqueous NaHCO3 solution
  5. washThe organic phase was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-94aed16badb146928363140882f07b43
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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