Isopropyl chloroformate → HCID 85471391, compound

HRID 713693Notes

Reaction equation

HRID 713693 reaction equation
NC1C=C2NC(C3C=C(N[C:19](C4OC(F)=CC=4)=[O:20])C=CC=3Cl)=NC2=NC=1.C(Cl)(=O)OC(C)C.[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41][C:42]([C:44]2[O:45][C:46](F)=[CH:47][CH:48]=2)=[O:43])=[CH:37][C:36]=1[C:50]1[N:51](C(OC(C)C)=O)[C:52]2[C:53]([N:65]=1)=[N:54][CH:55]=[C:56]([NH:58][C:59]([O:61][CH:62]([CH3:64])[CH3:63])=[O:60])[CH:57]=2.C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1>[CH:62]([O:61][C:59](=[O:60])[NH:58][C:56]1[CH:57]=[C:52]2[NH:51][C:50]([C:36]3[CH:37]=[C:38]([NH:41][C:42]([C:44]4[O:45][C:46]([O:20][CH3:19])=[CH:47][CH:48]=4)=[O:43])[CH:39]=[CH:40][C:35]=3[Cl:34])=[N:65][C:53]2=[N:54][CH:55]=1)([CH3:64])[CH3:63]

Participants

6

Reactant 4

HCID 7917Isopropyl chloroformateHCID 11430Potassium CarbonateHCID 90410680HCID 90410680, compoundHCID 90411433HCID 90411433, compound

Product 1

HCID 85471391HCID 85471391, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

In a 20 mL vial was transferred N-(3-(6-amino-1H-imidazo[4,5-b]pyridin-2-yl)-4-chlorophenyl)-5-fluorofuran-2-carboxamide (1-9) (60 mg, 0.161 mmol) in pyridine (2 mL), and the isopropyl carbonochloridate (1M solution, 0.241 mmols, 1.5 eq) was added. The brown reaction mixture was stirred at room temperature for 12 hrs. Checked via LCMS for the desired peak and found M+H (544) which seemed to be isopropyl 2-(2-chloro-5-(5-fluorofuran-2-carboxamido)phenyl)-6-((isopropoxycarbonyl)amino)-1H-imidazo[4,5-b]pyridine-1-carboxylate. Removed all solvents under vacuo and the reaction mixture was redissolved in MeOH (2 mL), and added potassium carbonate (55 mg, 0.402 mmols, 2.5 eq). The reaction mixture was heated at 60 C for 1 hr, checked via LCMS once more and found the M+H=470 as the only peak. The reaction mixture was filtered and the methanolic solution was then injected into the mass triggered HPLC to isolate the desired compound, treated with carbonate based resin and isolated the free base of Compound 39.

Workup

  1. customRemoved all solvents under vacuo
  2. dissolutionthe reaction mixture was redissolved in MeOH (2 mL)
  3. temperatureThe reaction mixture was heated at 60 C for 1 hr
  4. filtrationThe reaction mixture was filtered

Sources & evidence

ORD record
ord-274b6e7052664227812af7c31feca7a9
Source dataset
uspto-grants-2015_11
Patent number
US09186361B2

Reaction notes

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