1,2-Dichloroethane → HCID 67497658, compound

HRID 1628240Notes

Reaction equation

HRID 1628240 reaction equation
OC(C(F)(F)F)=O.[NH2:8][C@@H:9]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[C:10]([NH:12][C:13]1[N:17]([CH3:18])[N:16]=[C:15]([C:19]2[CH:24]=[CH:23][N:22]=[C:21]([CH3:25])[CH:20]=2)[CH:14]=1)=[O:11].CCN(C(C)C)C(C)C.S1C=C(C=O)N=C1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:64]CCCl>CC(O)=O>[ClH:64].[NH2:8][C@@H:9]([CH2:26][C:27]1[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=1)[C:10]([NH:12][C:13]1[N:17]([CH3:18])[N:16]=[C:15]([C:19]2[CH:24]=[CH:23][N:22]=[C:21]([CH3:25])[CH:20]=2)[CH:14]=1)=[O:11]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 2763214Thiazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 131731689HCID 131731689, compound

Product 1

HCID 67497658HCID 67497658, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
65 °C

Procedure

To a 100 ml flask was added (2S)-2-amino-3-(4-fluorophenyl)-N-(1-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-5-yl)propanamide TFA (85 mg, 0.182 mmoles), 5 ml of DCE, DIEA (48 μl, 0.27 mmole, Make sure pH=7), 50 ul of AcOH and thiazole-4-carbaldehyde (16 mg, 0.15 mmole). The reaction was stirred at 65° C. for 5 minutes at which time sodium triacetoxyborohydride (116 mg, 0.55 mmoles) was added and stirred at 65° C. for an additional 30 minutes. The solvent was then removed and the crude purified by reverse phase preparative HPLC to give (2S)-2-amino-3-(4-fluorophenyl)-N-(1-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-5-yl)propanamide HCl (27.8 mg, 34% yield) after salt exchange using 1 M HCl in ether (546 ul, 0.55 mmole). LCMS ESI (pos.) m/e: 451.1 (M+1): 1H NMR (500 MHz, MeOH-d) δ ppm 9.04 (d, J=1.22 Hz, 1H) 8.50 (d, J=6.11 Hz, 1H) 8.16 (s, 1H) 8.11 (d, J=6.11 Hz, 1H) 7.78 (s, 1H) 7.25 (dd, J=8.19, 5.26 Hz, 2H) 6.95-7.10 (m, 3H) 4.44 (s, 2H) 4.41 (dd, J=8.93, 5.99 Hz, 1H) 3.56 (s, 3H) 3.40 (dd, J=13.33, 5.50 Hz, 1H) 3.15 (dd, J=13.57, 9.41 Hz, 1H) 2.70 (s, 3H).

Workup

  1. additionwas added
  2. customThe solvent was then removed
  3. customthe crude purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-baa558d260c54005895ee12472dc115c
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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