Phosphoric Acid → HCID 86708588, compound

HRID 921715Notes

Reaction equation

HRID 921715 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH3:17])[C:12]3=[N:18][CH:19]=[C:20]([C:21]#[N:22])[N:11]3[N:10]=2)=[CH:6][C:5]([C:23]#[N:24])=[CH:4][C:3]=1[N:25]1[CH2:30][CH2:29][C@@H:28]([NH:31][C:32](=[O:35])[O:33][CH3:34])[C@H:27]([O:36][CH2:37]SC)[CH2:26]1.C1C(=O)N(I)C(=O)C1.[P:48](=[O:52])([OH:51])([OH:50])[OH:49].[O-]S([O-])(=S)=O.[Na+:58].[Na+].C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CO>[P:48]([O-:52])([O-:51])([O:50][CH2:37][O:36][C@H:27]1[C@H:28]([NH:31][C:32]([O:33][CH3:34])=[O:35])[CH2:29][CH2:30][N:25]([C:3]2[CH:4]=[C:5]([C:23]#[N:24])[CH:6]=[C:7]([NH:8][C:9]3[N:14]=[C:13]([NH:15][CH2:16][CH3:17])[C:12]4=[N:18][CH:19]=[C:20]([C:21]#[N:22])[N:11]4[N:10]=3)[C:2]=2[Cl:1])[CH2:26]1)=[O:49].[Na+:58].[Na+:58]

Participants

8

Reactant 5

HCID 1004Phosphoric AcidHCID 10340Sodium CarbonateHCID 24477Sodium ThiosulfateHCID 120273N-IodosuccinimideHCID 131732398HCID 131732398, compound

Product 1

HCID 86708588HCID 86708588, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-((methylthio)methoxy)piperidin-4-yl)carbamate (18 mg, 0.032 mmol) in THF (2 mL) at 0° C. was added NIS (14.18 mg, 0.063 mmol) followed by crystalline phosphoric acid (15.44 mg, 0.158 mmol) and allowed to warm to room temperature in 1 h. After TLC showed completion of starting material, reaction mixture was diluted with methanol (2 ml) and treated with 1M Na2S2O3 until it becomes colorless, then pH adjusted to 10 (approx) by addition of solid Na2CO3. Resultant precipitate was removed by filtration and submitted for LC-MS, which showed major product. The filtrate was concentrated and lyophilized to give crude off white solid. This was purified by reverse phase preparative HPLC to give pure sodium (((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl)oxy)methyl phosphate (9 mg) as an off white solid.

Workup

  1. customcompletion of starting material, reaction mixture
  2. customResultant precipitate was removed by filtration
  3. concentrationThe filtrate was concentrated
  4. customto give crude off white solid
  5. customThis was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-4c0a4fabe8e749bd84fd130554b8d34e
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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