Sodium sulfate decahydrate → HCID 86724130, compound

HRID 1748802Notes

Reaction equation

HRID 1748802 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[C:14]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[N:15][N:16]([CH2:26][CH3:27])[C:17]=2[NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:9][C:10](O)=[O:11])=[CH:4][CH:3]=1.BrC1C=CC(C=O)=CC=1.C(N1C(N)=CC(C2C=CC=CN=2)=N1)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>CCOCC>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[C:14]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[N:15][N:16]([CH2:26][CH3:27])[C:17]=2[NH:18][C:19](=[O:20])[O:21][C:22]([CH3:25])([CH3:23])[CH3:24])[CH2:9][CH2:10][OH:11])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 62649Sodium sulfate decahydrateHCID 707414-BromobenzaldehydeHCID 21226445Aluminium lithium hydride2×HCID 86724121HCID 86724121, compoundHCID 86724131HCID 86724131, compound

Product 1

HCID 86724130HCID 86724130, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

3-(4-Bromophenyl)-3-(5-((tert-butoxycarbonyl)amino)-1-ethyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)propanoic acid (0.786 g, 1.525 mmol, prepared using W from 4-bromobenzaldehyde, X from 1-ethyl-3-(pyridin-2-yl)-1H-pyrazol-5-amine then Y) was added in one portion to a mixture of LAH (0.232 g, 6.10 mmol) and Et2O (15.0 mL) under N2 at about 0° C. After about 1 h, the ice bath was removed. After stirring at rt for about 3 h, LAH (0.116 g, 3.05 mmol) was added in one portion. After about 2 h, the mixture was cooled to about 0° C. Sodium sulfate decahydrate was slowly added over about 15 min. After about 15 min, the ice bath was removed, the mixture was diluted with Et2O (20 mL), and then the mixture was left to vigorously stir for about 63 h. The mixture was filtered rinsing with Et2O (100 mL). The organic volatiles were removed under reduced pressure. The residue was purified on silica gel using a gradient of 50-75% EtOAc in heptane. The fractions containing product were combined and concentrated under reduced pressure to afford tert-butyl (4-(1-(4-bromophenyl)-3-hydroxypropyl)-1-ethyl-3-(pyridin-2-yl)-1H-pyrazol-5-yl)carbamate (0.359 g, 0.715 mmol, 47%) as a very pale yellow film. LC-MS (Table 1, Method g) Rt=2.45 min; m/z 501 and 503 (M+H)+; 1H NMR (400 MHz, DMSO) 8.82 (s, 1H), 8.59-8.52 (m, 1H), 7.89-7.72 (m, 2H), 7.39-7.18 (m, 5H), 5.02-4.87 (m, 1H), 4.61-4.45 (m, 1H), 3.97-3.86 (m, 2H), 3.36-3.22 (m, 1H), 2.36-2.04 (m, 2H), 1.43 (s, 9H), 1.43-1.21 (m, 3H).

Workup

  1. customthe ice bath was removed
  2. waitAfter about 2 h
  3. temperaturethe mixture was cooled to about 0° C
  4. waitAfter about 15 min
  5. customthe ice bath was removed
  6. additionthe mixture was diluted with Et2O (20 mL)
  7. waitthe mixture was left
  8. stirringto vigorously stir for about 63 h
  9. filtrationThe mixture was filtered
  10. washrinsing with Et2O (100 mL)
  11. customThe organic volatiles were removed under reduced pressure
  12. customThe residue was purified on silica gel using a gradient of 50-75% EtOAc in heptane
  13. additionThe fractions containing product
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d9c7b39990b648ddbbdc15a25e807918
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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