Thiazole-4-carboxaldehyde → HCID 67496202, compound

HRID 1628284Notes

Reaction equation

HRID 1628284 reaction equation
[NH2:1][C@@H:2]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:3]([NH:5][C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[CH:14]=1)[C:9]([OH:11])=[O:10])=[O:4].[S:28]1[CH:32]=[C:31](C=O)[N:30]=[CH:29]1.[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:22]1([CH2:21][C@H:2]([NH:1][CH2:35][C:32]2[S:28][CH:29]=[N:30][CH:31]=2)[C:3]([NH:5][C:6]2[CH:7]=[C:8]([CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[CH:14]=2)[C:9]([OH:11])=[O:10])=[O:4])[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 2763214Thiazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 67496640HCID 67496640, compound

Product 1

HCID 67496202HCID 67496202, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-3-(2-amino-3-phenylpropanamido)-5-(pyridin-4-yl)benzoic acid (45.1) (181 mg, 0.50 mmol) in DCM (5 mL) was added thiazole-4-carbaldehyde (56 mg, 0.50 mmol). The mixture was stirred for 1 h, sodium triacetoxyborohydride (212 mg, 1.00 mmol) was then added and the mixture stirred for an additional 1 hour at room temperature. The reaction mixture was then concentrated and the crude product purified by reverse phase chromatography (0-100% CH3CN/water+0.5% TFA) to afford (S)-3-(3-phenyl-2-(thiazol-5-ylmethylamino)propanamido)-5-(pyridin-4-yl)benzoic acid (45.2) as a white solid (82 mg, 36% yield). LCMS ESI (pos.) m/e: 459.0 (M+1). 1H NMR (500 MHz, MeOH-D4) δ ppm 9.13 (d, J=1.96 Hz, 1H), 8.93 (d, J=6.85 Hz, 2H), 8.35 (d, J=1.22 Hz, 1H), 8.32-8.34 (m, 2H), 8.31 (t, J=1.83 Hz, 1H), 8.18-8.23 (m, 1H), 7.82 (d, J=1.96 Hz, 1H), 7.23-7.37 (m, 5H), 4.48-4.58 (m, 2H), 4.35 (dd, J=9.29, 5.87 Hz, 1H), 3.41-3.51 (m, 1H), 3.24-3.30 (m, 1H).

Workup

  1. stirringthe mixture stirred for an additional 1 hour at room temperature
  2. concentrationThe reaction mixture was then concentrated
  3. customthe crude product purified by reverse phase chromatography (0-100% CH3CN/water+0.5% TFA)

Sources & evidence

ORD record
ord-f49ac240caf649be8e1e3c9b56187a53
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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