Dichloromethane → HCID 72950867, compound

HRID 1526796Notes

Reaction equation

HRID 1526796 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:36]=[C:37]([NH:39][C:40]2[NH:41][CH2:42][CH:43]([OH:46])[CH2:44][N:45]=2)[CH:38]=1)[C:5]([NH:7][CH2:8][C:9]([NH:11][C@H:12]([C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([C:29]([OH:35])([CH3:34])[C:30]([F:33])([F:32])[F:31])[CH:20]=1)[CH2:13][C:14]([O:16]CC)=[O:15])=[O:10])=[O:6].O.[OH-].[Li+].ClCCl>C(#N)C.O.O>[OH:1][C:2]1[CH:3]=[C:4]([CH:36]=[C:37]([NH:39][C:40]2[NH:45][CH2:44][CH:43]([OH:46])[CH2:42][N:41]=2)[CH:38]=1)[C:5]([NH:7][CH2:8][C:9]([NH:11][C@H:12]([C:19]1[CH:24]=[C:23]([C:25]([F:27])([F:28])[F:26])[CH:22]=[C:21]([C:29]([OH:35])([CH3:34])[C:30]([F:31])([F:32])[F:33])[CH:20]=1)[CH2:13][C:14]([OH:16])=[O:15])=[O:10])=[O:6]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 168937Lithium hydroxide, monohydrateHCID 86709967HCID 86709967, compound

Product 1

HCID 72950867HCID 72950867, compound

Reagents, catalysts & solvents 2

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

Procedure

To a suspension of (3S)-ethyl 3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido) acetamido)-3-(3-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-5-(trifluoromethyl)phenyl)propanoate (from step 2 above) (˜708 mmol, crude residue) in a mixture of acetonitrile/water (1:1) (6 mL) was added lithium hydroxide mono hydrate (150 mg, 3.575 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) 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 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 lyophilzation, as a colorless lyophilized powder (287.8 mg). LC-MS analysis of the solid shows the desired product's mass: m/z 636 (M+H); Calcd for C26H27F6N5O7: 635.51

Workup

  1. customThe solvent was evaporated in vacuo
  2. customto afford a yellow-orange viscous residue
  3. customto remove the urea
  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-3a00498448d14af998560279cb6481a1
Source dataset
uspto-grants-2015_07
Patent number
US09085606B2

Reaction notes

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