Acetic Acid → HCID 25160190, compound

HRID 914014Notes

Reaction equation

HRID 914014 reaction equation
C1([C:4]2[CH:5]=[C:6]3[C:10](=[C:11]([CH:13]([O:15][CH2:16][C:17]4([C:23]5[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=5)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[CH3:14])[CH:12]=2)[NH:9][N:8]=[CH:7]3)CC1.[C:30]([BH3-])#[N:31].[Na+].C=O.[C:36](O)(=O)C>C(#N)C.C(O)(=O)C>[F:29][C:26]1[CH:25]=[CH:24][C:23]([C:17]2([CH2:16][O:15][CH:13]([C:11]3[CH:12]=[C:4]([C:30]#[N:31])[CH:5]=[C:6]4[C:10]=3[NH:9][N:8]=[CH:7]4)[CH3:14])[CH2:22][CH2:21][N:20]([CH3:36])[CH2:19][CH2:18]2)=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 57546036HCID 57546036, compound

Product 1

HCID 25160190HCID 25160190, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a suspension of (±)-5-cyclopropyl-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-1H-indazole (21.8 mg, 0.055 mmol) and sodium cyanoborohydride (17.4 mg, 0.277 mmol) in acetonitrile (1 mL) at 0° C. was added formalin (0.041 mL). The reaction was treated with 1 drop of acetic acid. After 5 min, a second drop of acetic acid was added. The ice bath was removed and stirring continued for another hour. The reaction was diluted with diethyl ether and washed with 1 M sodium hydroxide. The ethereal was concentrated and loaded onto a strong cation exchange cartridge in methanol. The cartridge was flushed with several volumes of methanol which were discarded. The product was eluted with 2 M ammonia in methanol and concentrated. It was then purified by preparative HPLC to give 7.8 mg (55.7%). LC/MS (HPLC method 3): tR=1.742 min, 393.07(MH)+.

Workup

  1. customThe ice bath was removed
  2. waitcontinued for another hour
  3. additionThe reaction was diluted with diethyl ether
  4. washwashed with 1 M sodium hydroxide
  5. concentrationThe ethereal was concentrated
  6. customThe cartridge was flushed with several volumes of methanol which
  7. washThe product was eluted with 2 M ammonia in methanol
  8. concentrationconcentrated
  9. customIt was then purified by preparative HPLC
  10. customto give 7.8 mg (55.7%)

Sources & evidence

ORD record
ord-cb6dbacad6db404d8b9165141fd67928
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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