1-Hydroxybenzotriazole → HCID 91551434, compound

HRID 1863963Notes

Reaction equation

HRID 1863963 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH:46]([C:48]1[N:53]2[N:54]=[CH:55][N:56]=[C:52]2[CH:51]=[CH:50][N:49]=1)[NH2:47].C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])[CH2:10][C:11](=[O:13])[NH:47][NH:46][C:48]1[N:53]2[N:54]=[CH:55][N:56]=[C:52]2[CH:51]=[CH:50][N:49]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid2×HCID 34176375HCID 34176375, compound2×

Product 1

HCID 91551434HCID 91551434, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 133 mg (0.4 mmol) of (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (Intermediate 3), 84.5 mg (0.44 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 71 mg (0.5 mmol based on 95% purity) of 1-hydroxybenzotriazole (HOBT) in 1.5 mL of anhydrous DMF was stirred at room temperature in a stoppered flask. After 15 min, this solution was added dropwise by syringe through a septum to a stirred suspension of 72.1 mg (0.48 mmol) of 5-hydrazino[1,2,4]triazolo[1,5-c]pyrimidine (Intermediate 20) 0.209 mL (155 mg, 1.2 mmol) of N,N-diisopropylethylamine in 1 mL of anhydrous DMF. Stirring under nitrogen was continued for 17 h. The mixture was then filtered and concentrated under vacuum. The residue was partitioned between ethyl acetate and 5% aqueous citric acid solution. The organic phase was washed with more 5% citric acid, then with water, and finally with saturated aqueous sodium carbonate solution. The organic solution was dried over magnesium sulfate, filtered and concentrated to yield the title compound as an off-white solid, mp 207.5-209.5° C. LC-MS 488 (M+Na), 366 (M+1-Boc).

Workup

  1. waitwas continued for 17 h
  2. filtrationThe mixture was then filtered
  3. concentrationconcentrated under vacuum
  4. customThe residue was partitioned between ethyl acetate and 5% aqueous citric acid solution
  5. washThe organic phase was washed with more 5% citric acid
  6. dry with materialThe organic solution was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-f190cd26e4f34d4493fd84528b87d601
Source dataset
uspto-grants-2009_12
Patent number
US07625888B2

Reaction notes

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