Diisopropylethylamine → HCID 67391447, compound

HRID 1040557Notes

Reaction equation

HRID 1040557 reaction equation
[C:1]([C:3]1[CH:38]=[CH:37][C:6]([CH2:7][C@@:8]2([CH3:36])[N:12]3[C:13]([C:16]([NH:18][C@@H:19]([CH2:23][C:24]([NH2:26])=[O:25])[C:20]([OH:22])=O)=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:27]3[CH:32]=[C:31]([Cl:33])[CH:30]=[C:29]([Cl:34])[CH:28]=3)[C:9]2=[O:35])=[CH:5][CH:4]=1)#[N:2].Cl.[F:40][C:41]1([F:45])[CH2:44][NH:43][CH2:42]1.C1C=NC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O>[C:24]([CH2:23][C@H:19]([NH:18][C:16]([C:13]1[N:12]2[C@@:8]([CH2:7][C:6]3[CH:37]=[CH:38][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)([CH3:36])[C:9](=[O:35])[N:10]([C:27]3[CH:32]=[C:31]([Cl:33])[CH:30]=[C:29]([Cl:34])[CH:28]=3)[C:11]2=[N:15][CH:14]=1)=[O:17])[C:20]([N:43]1[CH2:44][C:41]([F:45])([F:40])[CH2:42]1)=[O:22])(=[O:25])[NH2:26]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67390583HCID 67390583, compound

Product 1

HCID 67391447HCID 67391447, compoundYield 45.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent4×

Procedure

A solution of the resulting intermediate (S)-2-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-succinamic acid (0.039 g, 0.070 mmol) in DMA (0.5 mL) was added to a solution of 3,3-difluoroazetidine hydrochloride (0.014 g, 0.135 mmol) in DMA (0.5 mL). A solution of HOAt (0.015 g, 0.110 mmol) in DMA (0.5 mL) was added to the reaction mixture, followed by HATU (0.04 g, 0.105 mmol) in 0.5 mL DMA. The reaction mixture was agitated on an orbital shaker for 3 h. Diisopropylethylamine (0.036 mL, 0.207 mmol) was added and the resulting solution was agitated on an orbital shaker for 14 h. The volatiles were removed in vacuo at 40° C. and the crude product was dissolved in DMSO (1 mL) and water (0.1 mL) and purified via reverse phase HPLC to afford 0.020 g (45%) of (R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid [(S)-1-carbamoylmethyl-2-(3,3-difluoro-azetidin-1-yl)-2-oxo-ethyl]-amide as a white solid, m/z 632.3 [M+1]+.

Workup

  1. stirringthe resulting solution was agitated on an orbital shaker for 14 h
  2. customThe volatiles were removed in vacuo at 40° C.
  3. dissolutionthe crude product was dissolved in DMSO (1 mL)
  4. customwater (0.1 mL) and purified via reverse phase HPLC

Sources & evidence

ORD record
ord-300c1dcd6f574b49868cf29322e135b5
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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