Dichloromethane → HCID 72950696, compound

HRID 1526791Notes

Reaction equation

HRID 1526791 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:16]([NH:23][C:24](=[O:44])[CH2:25][NH:26][C:27](=[O:43])[C:28]2[CH:33]=[C:32]([NH:34][C:35]3[NH:36][CH2:37][CH:38]([OH:41])[CH2:39][N:40]=3)[CH:31]=[C:30]([OH:42])[CH:29]=2)[CH2:17][C:18]([O:20]CC)=[O:19])[CH:5]=[C:6]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1.O.[OH-].[Li+].ClCCl>C(#N)C.O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:16]([NH:23][C:24](=[O:44])[CH2:25][NH:26][C:27](=[O:43])[C:28]2[CH:33]=[C:32]([NH:34][C:35]3[NH:40][CH2:39][CH:38]([OH:41])[CH2:37][N:36]=3)[CH:31]=[C:30]([OH:42])[CH:29]=2)[CH2:17][C:18]([OH:20])=[O:19])[CH:5]=[C:6]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 168937Lithium hydroxide, monohydrateHCID 86709957HCID 86709957, compound

Product 1

HCID 72950696HCID 72950696, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a suspension of (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 (from step 2 above) (0.842 mmol, crude residue) in a mixture of acetonitrile/water (1:1) (6 mL) was added lithium hydroxide monohydrate (180.0 mg, 4.289 mmol) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated in vacuo to afford a yellow-orange viscous residue. The residue was dissolved in water (25 mL) and stirred with dichloromethane (50 mL). The aqueous layer was separated and acidified with TFA (1 mL in 3 mL ACN) and evaporated in vacuo to afford a pale orange viscous residue. The crude residue was purified by reverse-phase preparative HPLC on a Biotage 40+M (100 g) C18HS column and a gradient 10-60% acetonitrile in water containing 0.05% TFA to give the desired product, after lyophilization, as a colorless lyophilized powder (305 mg). LC-MS analysis of the solid shows the desired product's mass: m/z 599 (35ClM+H) and m/z 601 (37ClM+H); Calcd for C28H31ClN6O7:599.03.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customto afford a yellow-orange viscous residue
  3. customThe aqueous layer was separated
  4. customevaporated in vacuo
  5. customto afford a pale orange viscous residue
  6. customThe crude residue was purified by reverse-phase preparative HPLC on a Biotage 40+M (100 g) C18HS column

Sources & evidence

ORD record
ord-51c4f0ba1c7d48e88d0d8fe5f47b60a6
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

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