Triethylamine → (3R)-3-(4-Cyanobenzyl)-1-(3,5-dichlorophenyl)-3-methyl-2-oxo-N-(1-{[2-(2H-tetrazol-5-yl)ethyl]carbamoyl}cyclopropyl)-2,3-dihydro-1H-imidazo[1,2-a]imidazole-5-carboxamide

HRID 1040534Notes

Reaction equation

HRID 1040534 reaction equation
[C:1]([C:3]1[CH:36]=[CH:35][C:6]([CH2:7][C@@:8]2([CH3:34])[N:12]3[C:13]([C:16]([NH:18][C:19]4([C:22](O)=[O:23])[CH2:21][CH2:20]4)=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:25]3[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=3)[C:9]2=[O:33])=[CH:5][CH:4]=1)#[N:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:61]1[C:65]([CH2:66][CH2:67][NH2:68])=[N:64][N:63]=[N:62]1.CCN(CC)CC>CN(C=O)C>[C:1]([C:3]1[CH:36]=[CH:35][C:6]([CH2:7][C@@:8]2([CH3:34])[N:12]3[C:13]([C:16]([NH:18][C:19]4([C:22](=[O:23])[NH:68][CH2:67][CH2:66][C:65]5[N:61]=[N:62][NH:63][N:64]=5)[CH2:20][CH2:21]4)=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:25]3[CH:26]=[C:27]([Cl:32])[CH:28]=[C:29]([Cl:31])[CH:30]=3)[C:9]2=[O:33])=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 584309681-{[(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}-cyclopropanecarboxylic acidHCID 178510901HCID 178510901, compound

Product 1

HCID 67390051(3R)-3-(4-Cyanobenzyl)-1-(3,5-dichlorophenyl)-3-methyl-2-oxo-N-(1-{[2-(2H-tetrazol-5-yl)ethyl]carbamoyl}cyclopropyl)-2,3-dihydro-1H-imidazo[1,2-a]imidazole-5-carboxamideYield 80.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-{[(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}-cyclopropanecarboxylic acid (50 mg, 0.09 mmol) and HATU (57 mg, 0.15 mmol), were combined with a heterogeneous solution of 2-(1H-tetrazol-5-yl)-ethylamine formiate (45 mg, 0.26 mmol) in anhydrous DMF (1 mL) and cooled to 0° C. Et3N (0.043 mL, 0.3 mmol) was added to the reaction. After 18 h the reaction slowly warmed to room temperature. The crude reaction solution was filtered and purified via reverse HPLC to yield 45 mg of the title compound as a white solid, m/z 619.5 [M+1]+).

Workup

  1. customAfter 18 h the reaction
  2. temperatureslowly warmed to room temperature
  3. customThe crude reaction solution
  4. filtrationwas filtered
  5. custompurified via reverse HPLC

Sources & evidence

ORD record
ord-5af222ba65c64080a1c3e9dcdb026f30
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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