Dichloromethane → HCID 72950694, compound

HRID 1526795Notes

Reaction equation

HRID 1526795 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:15]([NH:22][C:23](=[O:43])[CH2:24][NH:25][C:26](=[O:42])[C:27]2[CH:32]=[C:31]([NH:33][C:34]3[NH:35][CH2:36][CH:37]([OH:40])[CH2:38][N:39]=3)[CH:30]=[C:29]([OH:41])[CH:28]=2)[CH2:16][C:17]([O:19]CC)=[O:18])[CH:5]=[C:6]([C:8]([CH3:14])([CH3:13])[C:9]([F:12])([F:11])[F:10])[CH:7]=1.O.[OH-].[Li+].ClCCl>C(#N)C.O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:15]([NH:22][C:23](=[O:43])[CH2:24][NH:25][C:26](=[O:42])[C:27]2[CH:32]=[C:31]([NH:33][C:34]3[NH:39][CH2:38][CH:37]([OH:40])[CH2:36][N:35]=3)[CH:30]=[C:29]([OH:41])[CH:28]=2)[CH2:16][C:17]([OH:19])=[O:18])[CH:5]=[C:6]([C:8]([CH3:13])([CH3:14])[C:9]([F:12])([F:10])[F:11])[CH:7]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 168937Lithium hydroxide, monohydrateHCID 86709966HCID 86709966, compound

Product 1

HCID 72950694HCID 72950694, compound

Reagents, catalysts & solvents 2

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

Procedure

To a suspension of (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 (from step 2 above) (0.785 mmol, crude residue) in a mixture of acetonitrile/water (1:1) (6 mL) was added lithium hydroxide monohydrate (165 mg, 3.932 mmol) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated in vacuo to afford a yellow-orange viscous residue and the residue was dissolved in water (25 mL) and stirred with dichloromethane (50 mL) for 15 min. The aqueous layer was separated, acidified with TFA (1 mL in 3 mL ACN) and evaporated in vacuo to afford a pale 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 afford the desired product, after lyophilization, as a colorless lyophilized powder (277.7 mg). LC-MS analysis of the residue shows the desired product: (3S)-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)propanoic acid's mass: m/z 600 (35ClM+H), and m/z 602 (37ClM+H); Calcd for C26H29ClF3N5O6: 599.99.

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 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-67dbc3d41c21452596b8650097798c96
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

Loading…