Acetic Acid → HCID 67497638, compound

HRID 1628288Notes

Reaction equation

HRID 1628288 reaction equation
[NH2:1][C@@H:2]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:3]([NH:5][C:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)[CH:9]=[C:8]([Cl:19])[CH:7]=1)=[O:4].C(O)(=O)C.[N:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH:37]=O.C([BH3-])#N.[Na+].Cl>C(OC)(OC)OC.O>[Cl:19][C:8]1[CH:7]=[C:6]([NH:5][C:3](=[O:4])[C@@H:2]([NH:1][CH2:37][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][N:31]=2)[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)[CH:9]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 142732-PyridinecarboxaldehydeHCID 5003444Sodium cyanoborohydrideHCID 67496940HCID 67496940, compound

Product 1

HCID 67497638HCID 67497638, compoundYield 75.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 9005Trimethyl orthoformateSolvent

Procedure

(2S)-2-amino-N-(3-chloro-5-(2-methylpyridin-4-yl)phenyl)-3-phenylpropanamide (32 mg, 87 μmol) was dissolved in trimethyl thoformate (1 ml) and acetic acid (0.25 ml, 4367 μmol). To this was added picolinaldehyde (94 mg, 875 mmol). After 30 min sodium cyanoborohydride (82 mg, 1312 μmol) dissolved in trimethyl orthoformate (1 ml). After 1 h the reaction mixture was poured onto 1N HCl and water was added, the mixture was concentrated under reduced pressure. The resulting crude solid was dissolved in AcOH/DMSO and purified on Phenomenex Geminni C18 HPLC 50 mm×250 mm running ACN/Water/0.1% TFA in a linear gradient. The fractions containing the desired product were combined and concentrated to afford (2S)—N-(3-chloro-5-(2-methylpyridin-4-yl)phenyl)-3-phenyl-2-(pyridin-2-ylmethylamino)propanamide (46) (30 mg, 75% yield). MS ESI (pos.) m/e: 457.1 (M+H). 1H NMR (500 MHz) (CDCl3) δ 10.13 (1H, s), 8.68 (1H, d, J=6.1 Hz), 8.50 (1H, d, J=5.4 Hz), 7.99 (1H, dt, J=1.2, 9.0 Hz), 7.88 (1H, s), 7.72-7.77 (3H, m), 7.47-7.53 (2H, m), 7.34 (1H, m), 7.16-7.24 (6H, m), 4.28-4.36 (3H, m), 3.30 (1H, dd, J=5.8, 13.9 Hz), 3.14 (1H, dd, J=7.8, 13.7 Hz).

Workup

  1. additionwas added
  2. concentrationthe mixture was concentrated under reduced pressure
  3. dissolutionThe resulting crude solid was dissolved in AcOH/DMSO
  4. custompurified on Phenomenex Geminni C18 HPLC 50 mm×250 mm
  5. additionThe fractions containing the desired product
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-479d8ad9ca944a27a41e4f766531d76f
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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