Acetic Acid → Merck SIP Agonist

HRID 1268933Notes

Reaction equation

HRID 1268933 reaction equation
[CH3:1][CH:2]([CH3:23])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21]O)=[CH:17][CH:16]=3)[N:11]=2)=[CH:6][CH:5]=1.[NH:24]1[CH2:27][CH:26]([C:28]([OH:30])=[O:29])[CH2:25]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH3:1][CH:2]([CH3:23])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:16]=[CH:17][C:18]([CH2:21][N:24]4[CH2:27][CH:26]([C:28]([OH:30])=[O:29])[CH2:25]4)=[CH:19][CH:20]=3)[N:11]=2)=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 11645224[4-[5-[4-(2-Methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methanol

Product 1

HCID 10430549Merck SIP AgonistYield 74%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of 3.06 g (10.0 mmol) of Aldehyde 1, 1.06 g (10.5 mmol) of 3-azetidine carboxylic acid and 5 mL of acetic acid in 150 mL of methanol was stirred for 20 min at rt. A solution of sodium cyanoborohydride (380 mg, 5.0 mmol) in 20 mL of methanol was added. The reaction mixture was stirred for 1 h then was filtered. The solids were washed with 30 ml of methanol and dried to afford 2.88 g (74%) of the title compound: 1H NMR (400 Mhz, CD3OD) δ 0.95 (d, J=6.6, 6H), 1.96 (m, 1H), 2.62 (d, J=7.3, 2H), 3.42 (m, 1H), 4.19 (m, 4H), 4.41 (s, 2H), 7.43 (d, J=8.0, 2H), 7.64 (d, J=8.2, 2H), 8.14 (d, J=8.0, 2H), 8.23 (d, J=8.2, 2H); ESI-MS 392 (M+H); LC-1: 3.0 min.

Workup

  1. filtrationthen was filtered
  2. washThe solids were washed with 30 ml of methanol
  3. customdried

Sources & evidence

ORD record
ord-fbe47b1e6b884ac697340a2fc5989673
Source dataset
uspto-grants-2007_04
Patent number
US07199142B2

Reaction notes

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