1-Hydroxybenzotriazole hydrate → HCID 86709954, compound

HRID 1526788Notes

Reaction equation

HRID 1526788 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([C:42]#[N:43])[CH2:41][CH2:40][CH2:39]2)[CH:35]=[C:34]([Cl:44])[CH:33]=1)[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].O.ON1C2C=CC=CC=2N=N1>CN(C=O)C.C(Cl)Cl>[Cl: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([C:42]#[N:43])[CH2:41][CH2:40][CH2:39]2)[CH:35]=1

Participants

5

Reactant 3

HCID 27960291-Hydroxybenzotriazole hydrateHCID 69713030HCID 69713030, compoundHCID 86709955HCID 86709955, compound

Product 1

HCID 86709954HCID 86709954, 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) (314.5 mg, 1.02 mmol), ethyl (S)-3-amino-3-(3-chloro-5-(1-cyanocyclobutyl)phenyl)propanoate hydrochloride salt (from step 1 above) (345.15 mg, 1.006 mmol) and 1-hydroxybenzotriazole hydrate (31.2 mg, 0.204 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′-diisopropylcarbodiimde (225 μL, 1.453 mmol) was added to the above suspension and the reaction mixture was stirred at room temperature under nitrogen atmosphere overnight (19 h). The solvent was evaporated in vacuo to give a yellow-orange gummy residue. LC-MS analysis of the gummy residue shows the desired product: (3S)-ethyl 3-(3-chloro-5-(1-cyanocyclobutyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate's mass: m/z 597 (35ClM+H), m/z 599 (37ClM+H), m/z 619 (35ClM+Na) and m/z 621 (37ClM+Na); Calcd for C29H33ClN6O6: 597.06. The crude residue is used as such for the saponification with lithium hydroxide monohydrate (Step 3).

Workup

  1. customto give a cream suspension
  2. additionN,N′-diisopropylcarbodiimde (225 μL, 1.453 mmol) was added to the above suspension
  3. stirringthe reaction mixture was stirred at room temperature under nitrogen atmosphere overnight (19 h)
  4. customThe solvent was evaporated in vacuo
  5. customto give a yellow-orange gummy residue

Sources & evidence

ORD record
ord-ae3749e209714ff085097f0df0e885c0
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

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