Acetic Acid → HCID 178491069, compound

HRID 2402061Notes

Reaction equation

HRID 2402061 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:17]3[C:18]([CH3:28])=[N:19][N:20]4[CH:25]=[CH:24][C:23](C=O)=[CH:22][C:21]=34)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)=[CH:4][CH:3]=1.[C:31](O)(=O)C.C(Cl)Cl.[CH3:38][O:39][C:40]1[CH:47]=[C:46]([O:48][CH3:49])[CH:45]=[CH:44][C:41]=1[CH2:42][NH2:43].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:17]3[C:18]([CH3:28])=[N:19][N:20]4[CH:25]=[CH:24][C:23]([CH2:31][NH:43][CH2:42][C:41]5[CH:44]=[CH:45][C:46]([O:48][CH3:49])=[CH:47][C:40]=5[O:39][CH3:38])=[CH:22][C:21]=34)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 6

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 5972502,4-DimethoxybenzylamineHCID 5049666Sodium triacetoxyborohydrideHCID 178433750HCID 178433750, compound

Product 1

HCID 178491069HCID 178491069, compoundYield 62.3%

Procedure

To a suspension of 3-[4-(4-chlorobenzyl)-5-(4H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]-2-methylpyrazolo[1,5-a]pyridine-5-carbaldehyde (0.300 g, 0.690 mmol) in acetic acid (0.20 mL, 3.5 mmol) and dry methylene chloride (10 mL, 200 mmol) was added 2,4-dimethoxybenzylamine (0.207 mL, 1.38 mmol), followed by additional of sodium triacetoxyborohydride (0.363 g, 1.71 mmol). The mixture was stirred at rt. for 16 hours. The mixture was basified with NaHCO3 solution to ˜pH 8 then extracted with DCM. The DCM solution was washed with water. The crude product was purified by column chromatography (SiO2, elution with 0-100% MeOH in DCM) to afford a solid product (0.252 g, yield 62%). LCMS: (FA) ES+ 586, 588; ES− 584, 586. 1H NMR (400 MHz, CDCl3 and d4-methanol) δ: 8.23-8.25 (d, J=7.03 Hz, 1H), 8.18 (s, 1H), 8.01 (s, 1H), 7.28-7.30 (d, J=8.53 Hz, 2H), 7.09-7.11 (d, J=8.53 Hz, 2H), 7.01-7.03 (d, J=8.28 Hz, 1H), 6.78-6.80 (d, J=7.03 Hz, 1H), 6.33-6.37 (m, 2H), 4.53 (s, 2H), 3.65 (s, 2H), 3.64 (s, 6H), 3.61 (s, 2H), 2.61 (s, 3H).

Workup

  1. extractionthen extracted with DCM
  2. washThe DCM solution was washed with water
  3. customThe crude product was purified by column chromatography (SiO2, elution with 0-100% MeOH in DCM)

Sources & evidence

ORD record
ord-e2db3d581ded40b6851ca4d42616a782
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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