1-Hydroxybenzotriazole → HCID 178454286, compound

HRID 1497493Notes

Reaction equation

HRID 1497493 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9](=[N:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[NH:10][C:11]1[CH:31]=[CH:30][C:14]([C:15]([O:17][C:18]2[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26][C:27](O)=[O:28])=[CH:20][CH:19]=2)=[O:16])=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[C:41]([O:45][C:46]1[CH:61]=[CH:60][C:49]([CH2:50][C@@H:51]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[NH2:52])=[CH:48][CH:47]=1)([CH3:44])([CH3:43])[CH3:42].Cl.CN(C)CCCN=C=NCC.N1(O)C2C=CC=CC=2N=N1>CN(C)C=O.O.C(N(CC)CC)C>[C:36]([O:35][C:33]([NH:32][C:9](=[N:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[NH:10][C:11]1[CH:12]=[CH:13][C:14]([C:15]([O:17][C:18]2[CH:19]=[CH:20][C:21]([CH2:24][CH2:25][CH2:26][C:27]([NH:52][C@H:51]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:50][C:49]3[CH:60]=[CH:61][C:46]([O:45][C:41]([CH3:43])([CH3:42])[CH3:44])=[CH:47][CH:48]=3)=[O:28])=[CH:22][CH:23]=2)=[O:16])=[CH:30][CH:31]=1)=[O:34])([CH3:38])([CH3:39])[CH3:37]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16219019(S)-tert-Butyl 2-amino-3-(4-(tert-butoxy)phenyl)propanoate hydrochlorideHCID 178454287HCID 178454287, compound

Product 1

HCID 178454286HCID 178454286, compoundYield 86.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 4-[4-({4-[N′,N″-bis(tert-butoxycarbonyl)carbamimidamido]benzoyl}oxy)phenyl]butanoic acid (250 mg) in N,N-dimethylformamide (5.00 mL) were added tert-butyl O-tert-butyl-L-tyrosinate hydrochloride (152 mg), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (88.5 mg), 1H-benzotriazol-1-ol (62.4 mg), and triethylamine (0.0643 mL), followed by stirring at room temperature overnight. To a reaction solution was added water, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution in this order, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain tert-butyl N-{4-[4-({4-[N′,N″-bis(tert-butoxycarbonyl)carbamimidamido]benzoyl}oxy)phenyl]butanoyl}-O-tert-butyl-L-tyrosinate (327 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with water
  3. dry with materiala saturated aqueous sodium chloride solution in this order, then dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-00e6b0bc208f4e9fbe1fb720b6996d1b
Source dataset
uspto-grants-2015_12
Patent number
US09199927B2

Reaction notes

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