Diisopropylethylamine → HCID 23554393, compound

HRID 988453Notes

Reaction equation

HRID 988453 reaction equation
C1C=CC2N(O)N=NC=2C=1.O.C(N(CC)C(C)C)(C)C.[CH3:21][C@H:22]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:23]([OH:25])=O.Cl.CN(C)CCCN=C=NCC.[NH2:46][CH:47]1[N:53]=[C:52]([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C:51]2[CH:60]=[CH:61][CH:62]=[CH:63][C:50]=2[N:49]([CH2:64][CH2:65][CH2:66][C:67]([F:70])([F:69])[F:68])[C:48]1=[O:71]>C1COCC1.C(Cl)Cl>[C:30]([O:29][C:27]([NH:26][C@H:22]([C:23]([NH:46][CH:47]1[N:53]=[C:52]([C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=2)[C:51]2[CH:60]=[CH:61][CH:62]=[CH:63][C:50]=2[N:49]([CH2:64][CH2:65][CH2:66][C:67]([F:69])([F:68])[F:70])[C:48]1=[O:71])=[O:25])[CH3:21])=[O:28])([CH3:33])([CH3:32])[CH3:31]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22392916HCID 22392916, compound

Product 1

HCID 23554393HCID 23554393, compoundYield 87.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of HOBt-H2O (373 mg, 2.76 mmol), N,N-diisopropylethylamine (481 uL, 2.76 mmol) and N-t-BOC-L-alanine (522 mg, 2.76 mmol) in 10 mL of anhydrous THF at 0° C. was added 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDCI; 527 mg, 2.76 mmol) in one portion. After stirring 5 min., a solution of 3-amino-2,3-dihydro-1-(4,4,4-trifluorobutyl)-5-phenyl-1H-1,4-benzodiazepin-2-one (1.05 g, 2.91 mmol) in 10 mL of anhydrous THF was added via syringe and the reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was diluted with 100 mL methylene chloride, extracted sequentially with 10% citric acid, saturated sodium bicarbonate, water and brine and then dried over sodium sulfate. Purification of the crude product using silica gel chromatography (10%-30% ethyl acetate/methylene chloride) gave 1.28 g (83%) of a white foam.

Workup

  1. stirringstirred overnight
  2. extractionextracted sequentially with 10% citric acid, saturated sodium bicarbonate, water and brine
  3. dry with materialdried over sodium sulfate
  4. customPurification of the crude product

Sources & evidence

ORD record
ord-203dc327ee204b2bbf83c2e489408f16
Source dataset
uspto-grants-2003_10
Patent number
US06635632B1

Reaction notes

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