Diisopropylcarbodiimide → HCID 86709971, compound

HRID 1526798Notes

Reaction equation

HRID 1526798 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([NH:15][C:16]2[NH:17][CH2:18][CH:19]([OH:22])[CH2:20][N:21]=2)[CH:14]=1)[C:5]([NH:7][CH2:8][C:9]([OH:11])=O)=[O:6].Cl.[NH2:24][C@H:25]([C:32]1[CH:37]=[C:36]([C:38]2([CH:41]([F:43])[F:42])[CH2:40][CH2:39]2)[CH:35]=[C:34]([Br:44])[CH:33]=1)[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].O.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C>CN(C=O)C.C(Cl)Cl>[Br:44][C:34]1[CH:33]=[C:32]([C@@H:25]([NH:24][C:9](=[O:11])[CH2:8][NH:7][C:5](=[O:6])[C:4]2[CH:12]=[C:13]([NH:15][C:16]3[NH:17][CH2:18][CH:19]([OH:22])[CH2:20][N:21]=3)[CH:14]=[C:2]([OH:1])[CH:3]=2)[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:37]=[C:36]([C:38]2([CH:41]([F:43])[F:42])[CH2:39][CH2:40]2)[CH:35]=1

Participants

6

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 69713030HCID 69713030, compoundHCID 86709968HCID 86709968, compound

Product 1

HCID 86709971HCID 86709971, compound

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A mixture of 2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetic acid (Example B) (197.22 mg, 0.64 mmol), (S)-ethyl 3-amino-3-(3-bromo-5-(1-(difluoromethyl)cyclopropyl)phenyl)propanoate hydrochloride salt (from step 1 above) (253 mg, 0.635 mmol) and 1-hydroxybenzotriazole hydrate (19.44 mg, 0.127 mmol) was dissolved in a mixture of DMF/DCM (1:1) (8 mL) and stirred at room temperature under nitrogen atmosphere for 10 min to give a cream suspension. N,N′-diisopropylcarbodiimide (142 μL, 0.917 mmol) was added to the above suspension and the reaction mixture was stirred at room temperature overnight (16 h) under nitrogen atmosphere. The solvent was evaporated in vacuo to give a yellow gummy residue of the intermediate product. LC-MS analysis shows the desired product: (3S)-ethyl 3-(3-bromo-5-(1-(difluoromethyl)cyclopropyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate's mass: m/z 652 (79BrM+H), m/z 654 (81BrM+H). The crude residue will be used as such for the saponification with lithium hydroxide monohydrate (Step 3).

Workup

  1. customto give a cream suspension
  2. stirringthe reaction mixture was stirred at room temperature overnight (16 h) under nitrogen atmosphere
  3. customThe solvent was evaporated in vacuo
  4. customto give a yellow gummy residue of the intermediate product

Sources & evidence

ORD record
ord-143f20707aec4fa5925e471a206ba16e
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

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