Acetic Acid → HCID 57545947, compound

HRID 913953Notes

Reaction equation

HRID 913953 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:12]=O)[C:8]2[C:4](=[CH:5][N:6]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:7]=2)[CH:3]=1.[CH3:44][NH:45][CH3:46].C([BH3-])#N.[Na+].CC(O)=O>C(#N)C.CC(O)=O>[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:14][CH2:15][C:16]2([C:29]3[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=3)[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[CH2:20][CH2:21]2)[CH2:12][N:45]([CH3:46])[CH3:44])[C:8]2[C:4](=[CH:5][N:6]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:41])[CH3:42])[N:7]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 674DimethylamineHCID 5003444Sodium cyanoborohydrideHCID 57546061HCID 57546061, compound

Product 1

HCID 57545947HCID 57545947, compoundYield 65.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (40.0 mg, 0.063 mmol)and DIMETHYLAMINE (0.040 mL, 0.316 mmol) in Acetonitrile (1.5 mL) at 0° C. was added SODIUM CYANOBOROHYDRIDE (3.98 mg, 0.063 mmol). To this was added 1 drop of HOAc, and a second drop of HOAc after 5 min. The reaction was then stirred at R.T. for another hour. LC/MS showed reaction complete. It was concentrated, diluted with ether and washed with 0.5M NaOH, then loaded onto an SCX cartridge in methanol. The cartridge was flushed with several volumes of methanol which were discarded, and eluted with 2M NH3 in MeOH, the solvent was concentrated to give the title product (27 mg, 0.041 mmol, 64.5% yield). 1H-NMR (CDCl3, 500 MHz) δ 7.99 (s, 1H),), 7.48 (d, J=1.83 Hz, 1H), 7.29 (m, 2H), 7.03 (m, 2H), 6.61 (d, J=19.8 Hz, 1H), 5.64 (m, 2H), 5.05 (m, 1H), 3.63 (m, 2H), 3.60 (t, c), 3.4 (m, 1H), 3.31 (m, 1H), 3.04 (m, 2H), 2.9 (m, 1H), 2.7 (m, 1H), 2.6 (m,2H), 2.25 (d, J=2.44 Hz, 6H), 2.2 (m, 1H), 2.05 (m, 1H), 1.9 (m, 1H), 1.8 (m, 1H), 1.43 (s, 9H), 0.9 (t, J=8.55 Hz, 2H), 0.06 (s, 9H). LC/MS (HPLC method 3): tR=3.53 min, 661.5(MH)+.

Workup

  1. customreaction complete
  2. concentrationIt was concentrated
  3. additiondiluted with ether
  4. washwashed with 0.5M NaOH
  5. customThe cartridge was flushed with several volumes of methanol which
  6. washeluted with 2M NH3 in MeOH
  7. concentrationthe solvent was concentrated

Sources & evidence

ORD record
ord-4defc3c60ac24cdc939fe4774368f1c1
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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