Formaldehyde → HCID 90029424, compound

HRID 2200208Notes

Reaction equation

HRID 2200208 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:7]=[C:8]([NH:16][C:17]([NH:19][C:20]3[CH:38]=[CH:37][C:23]([O:24][C:25]4[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32]([CH:34]5[CH2:36][CH2:35]5)=[O:33])[CH:26]=4)=[CH:22][CH:21]=3)=[O:18])[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=2)[CH2:2]1.C=O.O.[C:42]([O-])(O)=O.[Na+]>CO>[CH3:42][N:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:7]=[C:8]([NH:16][C:17]([NH:19][C:20]3[CH:21]=[CH:22][C:23]([O:24][C:25]4[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32]([CH:34]5[CH2:35][CH2:36]5)=[O:33])[CH:26]=4)=[CH:37][CH:38]=3)=[O:18])[CH:9]=[C:10]([C:12]([F:14])([F:13])[F:15])[CH:11]=2)[CH2:2]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 516892Sodium BicarbonateHCID 90020623HCID 90020623, compound

Product 1

HCID 90029424HCID 90029424, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dissolve N-[4-[4-[[3-(azetidin-3-yloxy)-5-(trifluoromethyl)phenyl]carbamoylamino]-phenoxy]-2-pyridyl]cyclopropanecarboxamide (210 mg, 0.4 mmol) in methanol (10 mL), add 35% aqueous formaldehyde solution (205 mg, 2.39 mmol), sitr for 1.5 hrs. Add Na(CN)BH3 (150 mg, 2.39 mmol) and stir at room temperature for 3 hrs. After reaction, pour the reaction mixture to water (50 mL), adjust pH=7 with saturated NaHCO3 solution, extract with EtOAc (15 mL×3), combine the organic layers, wash with brine (100 mL), dry over anhydrous Na2SO4. Concentrate under reduced pressure to give the crude product. Purification by chromatography (silica gel, DCM:MeOH=20:1) affords the target compound (16 mg, 7%). MS: (M+1): 542.3.

Workup

  1. customAfter reaction
  2. extractionextract with EtOAc (15 mL×3)
  3. washwash with brine (100 mL)
  4. dry with materialdry over anhydrous Na2SO4
  5. concentrationConcentrate under reduced pressure
  6. customto give the crude product
  7. customPurification by chromatography (silica gel, DCM:MeOH=20:1)

Sources & evidence

ORD record
ord-9222419e447748aaa27e3a2d7a243d77
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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