Diisopropylcarbodiimide → HCID 86709957, compound

HRID 1526790Notes

Reaction equation

HRID 1526790 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.[CH2:24]([O:26][C:27](=[O:46])[CH2:28][C@H:29]([NH2:45])[C:30]1[CH:35]=[C:34]([C:36]2([C:42]#[N:43])[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)[CH:33]=[C:32]([Cl:44])[CH:31]=1)[CH3:25].O.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C>CN(C=O)C.C(Cl)Cl>[Cl:44][C:32]1[CH:31]=[C:30]([C@@H:29]([NH:45][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)[CH2:28][C:27]([O:26][CH2:24][CH3:25])=[O:46])[CH:35]=[C:34]([C:36]2([C:42]#[N:43])[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)[CH:33]=1

Participants

6

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 69713030HCID 69713030, compoundHCID 86709958HCID 86709958, compound

Product 1

HCID 86709957HCID 86709957, 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) (264.7 mg, 0.859 mmol), (S)-ethyl-3-amino-3-(3-chloro-5-(4-cyanotetrahydro-2H-pyran-4-yl)phenyl)propanoate hydrochloride salt (from step 1 above) (314.3 mg, 0.842 mmol) and 1-hydroxybenzotriazole hydrate (27.4 mg, 0.179 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. Neat N,N′-diisopropylcarbodiimide (175 μL, 1.13 mmol) was added to the above suspension and the reaction mixture was stirred at room temperature under nitrogen atmosphere overnight. The solvent was evaporated in vacuo to give a pale yellow-cream gummy residue. LC-MS analysis of the crude residue shows the desired product: (3S)-ethyl 3-(3-chloro-5-(4-cyanotetrahydro-2H-pyran-4-yl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate's mass: m/z 627 (35ClM+H) and m/z 629 (37ClM+H); Calcd for C30H35ClN6O7: 627.09. The crude residue is 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 under nitrogen atmosphere overnight
  3. customThe solvent was evaporated in vacuo
  4. customto give a pale yellow-cream gummy residue

Sources & evidence

ORD record
ord-9f00b7fa8ea2409eb98e39fef83218d2
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

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