Acetic Acid → HCID 178482066, compound

HRID 1628257Notes

Reaction equation

HRID 1628257 reaction equation
[NH2:1][C@@H:2]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[C:3]([NH:5][C:6]1[N:10]([CH3:11])[N:9]=[C:8]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][CH3:19])[CH:13]=2)[CH:7]=1)=[O:4].[NH:28]1[CH:32]=[CH:31][C:30]([CH:33]=O)=[N:29]1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>O1CCOCC1.ClCCCl>[NH:28]1[CH:32]=[CH:31][C:30]([CH2:33][NH:1][C@@H:2]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)[C:3]([NH:5][C:6]2[N:10]([CH3:11])[N:9]=[C:8]([C:12]3[CH:17]=[CH:16][N:15]=[C:14]([NH:18][CH3:19])[CH:13]=3)[CH:7]=2)=[O:4])=[N:29]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 122183831H-Pyrazole-3-carbaldehydeHCID 67496348HCID 67496348, compound

Product 1

HCID 178482066HCID 178482066, compoundYield 28.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To (2S)-2-amino-3-(4-fluorophenyl)-N-(1-methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)propanamide (79 mg, 214 μmol) was added 1H-pyrazole-3-carbaldehyde (29 mg, 300 μmol), then DCE and dioxane were added as solvents, followed by acetic acid (13 μl, 225 μmol) and NaBH(OAc)3 (136 mg, 643 μmol). Heating was continued for 1 hr. 40 min. The reaction was concentrated and purified by reverse phase HPLC purification to afford 23.2 (27 mg, 28%) as a white solid. 1H NMR (400 MHz, MeOH) δ ppm 7.77-8.01 (m, 1H) 7.55 (br. s., 1H) 7.25 (dd, J=8.61, 5.48 Hz, 2H) 7.03 (t, J=8.80 Hz, 2H) 6.91 (dd, J=5.67, 1.37 Hz, 1H) 6.51-6.65 (m, 1H) 6.23 (d, J=1.96 Hz, 1H) 3.74-3.91 (m, 2H) 3.60-3.63 (m, 1H) 3.59 (s, 3H) 2.97-3.11 (m, 2H) 2.89 (s, 3H).

Workup

  1. temperatureHeating
  2. custom40 min
  3. concentrationThe reaction was concentrated
  4. custompurified by reverse phase HPLC purification

Sources & evidence

ORD record
ord-3025d21ec186430d8e8dbd75542dffa9
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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