Dichloromethane → HCID 72721008, compound

HRID 1526799Notes

Reaction equation

HRID 1526799 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@@H:14]([NH:21][C:22](=[O:42])[CH2:23][NH:24][C:25](=[O:41])[C:26]2[CH:31]=[C:30]([NH:32][C:33]3[NH:34][CH2:35][CH:36]([OH:39])[CH2:37][N:38]=3)[CH:29]=[C:28]([OH:40])[CH:27]=2)[CH2:15][C:16]([O:18]CC)=[O:17])[CH:5]=[C:6]([C:8]2([CH:11]([F:13])[F:12])[CH2:10][CH2:9]2)[CH:7]=1.O.[OH-].[Li+].ClCCl>C(#N)C.O.O>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:14]([NH:21][C:22](=[O:42])[CH2:23][NH:24][C:25](=[O:41])[C:26]2[CH:31]=[C:30]([NH:32][C:33]3[NH:38][CH2:37][CH:36]([OH:39])[CH2:35][N:34]=3)[CH:29]=[C:28]([OH:40])[CH:27]=2)[CH2:15][C:16]([OH:18])=[O:17])[CH:5]=[C:6]([C:8]2([CH:11]([F:13])[F:12])[CH2:10][CH2:9]2)[CH:7]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 168937Lithium hydroxide, monohydrateHCID 86709971HCID 86709971, compound

Product 1

HCID 72721008HCID 72721008, compound

Reagents, catalysts & solvents 2

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

Procedure

To a suspension of (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 (from step 2 above) (0.635 mmol, crude residue) in a mixture of acetonitrile/water (1:1) (6 mL) was added lithium hydroxide monohydrate (135 mg, 3.217 mmol) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated in vacuo to afford a pale yellow crystalline residue. The residue was dissolved in water (25 mL) and stirred with dichloromethane (50 mL) to remove the urea. The aqueous layer was neutralized with TFA (1 mL in 3 mL ACN) and evaporated in vacuo to afford a pale yellow 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 (94.0 mg). LC-MS analysis of the product shows the desired product's mass: m/z 624 (79BrM+H) and m/z 626 (81BrM+H); Calcd for C26H28BrF2N5O6: 624.43.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customto afford a pale yellow crystalline residue
  3. customto remove the urea
  4. customevaporated in vacuo
  5. customto afford a pale yellow 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-92cee9fcddf94c1a8526336b1e8513a6
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

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