1-Hydroxybenzotriazole hydrate → HCID 86709960, compound

HRID 1526792Notes

Reaction equation

HRID 1526792 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]([OH:44])([CH3:43])[C:39]([F:42])([F:41])[F:40])[CH:35]=[C:34]([Cl:45])[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:45][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]([OH:44])([CH3:43])[C:39]([F:42])([F:41])[F:40])[CH:35]=1

Participants

5

Reactant 3

HCID 27960291-Hydroxybenzotriazole hydrateHCID 69713030HCID 69713030, compoundHCID 86709961HCID 86709961, compound

Product 1

HCID 86709960HCID 86709960, 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) (328.3 mg, 1.065 mmol), (3S)-ethyl 3-amino-3-(3-chloro-5-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)propanoate hydrochloride salt (from step 1 above) (364.2 mg, 0.968 mmol) and 1-hydroxybenzotriazole hydrate (31.5 mg, 0.206 mmol) was dissolved in a mixture of DMF/DCM (1:1) and stirred at room temperature under nitrogen atmosphere for 10 min to give a cream suspension. N,N′-diisopropylcarbodiimde (210 μL, 1.356 mmol) was added to the above suspension and the reaction mixture was stirred at room temperature overnight (19 h) under nitrogen atmosphere. The solvent was evaporated in vacuo to give a yellow-cream gummy residue. LC-MS analysis of the crude residue shows the desired product: (3S)-ethyl 3-(3-chloro-5-(1,1,1-trifluoro-2-methylpropan-2-yl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate's mass: m/z 630 (35ClM+H) and m/z 632 (37ClM+H); Calcd for C27H31ClF3N5O7: 630.01. 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 (210 μL, 1.356 mmol) was added to the above suspension
  3. stirringthe reaction mixture was stirred at room temperature overnight (19 h) under nitrogen atmosphere
  4. customThe solvent was evaporated in vacuo
  5. customto give a yellow-cream gummy residue

Sources & evidence

ORD record
ord-599a7d22c74c426f9344cef53d564066
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

Loading…