Acetic Acid → HCID 50904992, compound

HRID 872281Notes

Reaction equation

HRID 872281 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[O:15][C:16]1[C:21]([CH:22]=O)=[CH:20][C:19]([Cl:24])=[CH:18][N:17]=1.[CH3:25][S:26]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)(=[O:28])=[O:27].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[Br:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[O:15][C:16]1[C:21]([CH2:22][N:32]2[CH2:33][CH2:34][N:29]([S:26]([CH3:25])(=[O:28])=[O:27])[CH2:30][CH2:31]2)=[CH:20][C:19]([Cl:24])=[CH:18][N:17]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7091611-(Methylsulfonyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 86666458HCID 86666458, compound

Product 1

HCID 50904992HCID 50904992, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

2-{[4-bromo-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]oxy}-5-chloropyridine-3-carbaldehyde (32, 2.60 g, 6.38 mmol) was dissolved in anhydrous dichloroethane (63.8 mL, 0.1M) and treated with 1-(methylsulfonyl)piperazine (2.10 g, 12.8 mmol, 2 equiv.) and acetic acid (3.65 mL, 63.8 mmol, 10 equiv.). After 30 minutes the solution formed a thick suspension and was treated with sodium triacetoxyborohydride (1.76 g, 8.29 mmol, 1.3 equiv) in small portions over 1 hour. After completion of this addition, the reaction was allowed to stir an additional 2 h at ambient temperature. Upon completion as judged by TLC and LCMS, the reaction was quenched by the slow addition of water (20 mL) and NaHCO3. The mixture was extracted 3× with dichloromethane (3×30 mL), and the combined organic layers were dried over MgSO4. The crude mixture was purified using flash column chromatography (Redisep SiO2, 80 g, 0-100% EtOAc/hexanes) to provide pure 198: 1H NMR (300 MHz, CDCl3) δ 7.89 (d, 1H, J=2.5 Hz), 7.84 (d, 1H, J=2.5 Hz), 7.56 (d, 1H, J=8.8 Hz), 7.33 (d, 1H, 8.8 Hz), 4.53 (d, 2H, J=7.1 Hz), 3.82 (s, 2H), 3.33 (m, 4H), 2.83 (s, 3H), 2.74 (m, 4H), 1.41 (m, 1H), 0.69 (m, 2H), 0.52 (dd, 2H, J=10.8, 5.1 Hz, 2H). LRMS m/z (M+H) 556.9 found, 556.9 required.

Workup

  1. customAfter 30 minutes the solution formed a thick suspension
  2. additionAfter completion of this addition
  3. customthe reaction was quenched by the slow addition of water (20 mL) and NaHCO3
  4. extractionThe mixture was extracted 3× with dichloromethane (3×30 mL)
  5. dry with materialthe combined organic layers were dried over MgSO4
  6. customThe crude mixture was purified
  7. customto provide pure 198

Sources & evidence

ORD record
ord-7d287bbf67a84932b7b58e0cb2f797c1
Source dataset
uspto-grants-2015_03
Patent number
US08975286B2

Reaction notes

Loading…