Acetic Acid → 1-((3-Methyl-4-(5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylic acid

HRID 1177459Notes

Reaction equation

HRID 1177459 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C:10]1[S:11][C:12]2[C:17]([N:18]=1)=[CH:16][CH:15]=[C:14]([C:19]1([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:21][CH2:20]1)[N:13]=2)[CH:5]=O.[NH:28]1[CH2:31][CH:30]([C:32]([OH:34])=[O:33])[CH2:29]1.C(O)(=O)C.C([BH3-])#N.[Na+]>C(Cl)Cl.CO>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:5][N:28]2[CH2:31][CH:30]([C:32]([OH:34])=[O:33])[CH2:29]2)[CH:7]=[CH:8][C:9]=1[C:10]1[S:11][C:12]2[C:17]([N:18]=1)=[CH:16][CH:15]=[C:14]([C:19]1([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:20][CH2:21]1)[N:13]=2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 866387133-Methyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)benzaldehyde

Product 1

HCID 446011051-((3-Methyl-4-(5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)azetidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 3-methyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)-benzaldehyde (85.0 mg, 229 μmol), azetidine-3-carboxylic acid (116 mg, 1147 μmol), and acetic acid (106 μL, 1836 μmol) in 1:1 CH2Cl2/MeOH (7.0 mL) was stirred at 25° C. for 1 h. Sodium cyanoborohydride (26 mg, 413 μmol) was then added, and the resulting mixture was stirred at 25° C. for 16 h. The reaction mixture was then concentrated in vacuo, dissolved in 2 mL DMSO+20 μL trifluoroacetic acid, filtered, and purified by rpHPLC (10-100% acetonitrile/water+0.1% TFA) to provide 1-((3-methyl-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)methyl)-azetidine-3-carboxylic acid as a white solid. MS (ESI) m/z: Calculated: 455.2; Observed: 456.1 (M++1). 1H NMR (400 MHz, MeOH) δ ppm 8.11 (d, J=8.6 Hz, 1 H), 7.88 (d, J=7.8 Hz, 1 H), 7.35-7.55 (m, 6 H), 7.27-7.34 (m, 1 H), 7.11 (d, J=8.6 Hz, 1 H), 4.47 (s, 2 H), 4.32-4.42 (m, 4 H), 3.63-3.81 (m, 1 H), 2.67 (s, 3 H), 1.70-1.77 (m, 2 H), 1.36-1.47 (m, 2 H)

Workup

  1. stirringthe resulting mixture was stirred at 25° C. for 16 h
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. dissolutiondissolved in 2 mL DMSO+20 μL trifluoroacetic acid
  4. filtrationfiltered
  5. custompurified by rpHPLC (10-100% acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-c2d52ed9cdc34608ad7f8e6f319d2108
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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