1,2-Dichloroethane → HCID 67497514, compound

HRID 1628241Notes

Reaction equation

HRID 1628241 reaction equation
[NH2:1][C@@H:2]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=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]([CH3:18])[CH:13]=2)[CH:7]=1)=[O:4].CCN(C(C)C)C(C)C.O.[C:37]([OH:41])(=[O:40])[CH:38]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:56]CCCl>CC(O)=O>[ClH:56].[ClH:56].[F:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][C@H:2]([NH:1][CH2:38][C:37]([OH:41])=[O:40])[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]([CH3:18])[CH:13]=3)[CH:7]=2)=[O:4])=[CH:25][CH:24]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 15620607Glyoxylic acid, monohydrateHCID 67496973HCID 67496973, compound

Product 1

HCID 67497514HCID 67497514, compound

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 diTFA (120 mg, 0.21 mmole), 3 ml of DCE, DIEA (90 μl, 0.52 mmole, make sure pH=7), 75 μl of AcOH and glyoxylic acid monohydrate (19 mg, 0.21 mmole). The reaction was stirred at 65° C. for 5 minutes at which time was added sodium triacetoxyborohydride (131 mg, 0.62 mmole) and stirred at 65° C. for an additional 18 hours. The solvent was then removed and the crude purified by reverse phase preparative HPLC to give 2-((S)-3-(4-fluorophenyl)-1-(1-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid dihydrochloride 16.2 as a yellow solid (20.7 mg, 21 mmol, yield) after salt exchange using 4 M HCl in dioxane (155 μl, 0.62 mmole). LCMS ESI (pos.) m/e: 412.1 (M+1): 1H NMR (400 MHz, MeOH) δ ppm 8.61 (d, J=6.26 Hz, 1H), 8.21 (d, J=6.65 Hz, 1H), 8.26 (s, 1H), 7.39 (dd, J=8.41, 5.28 Hz, 2H), 7.07-7.20 (m, 3H), 4.52 (br. s., 1H), 3.94-4.06 (m, 2H), 3.67-3.70 (m, 3H), 3.46 (m, 1H), 3.29 (m, 1H), 2.80 (s, 3H).

Workup

  1. stirringstirred at 65° C. for an additional 18 hours
  2. customThe solvent was then removed
  3. customthe crude purified by reverse phase preparative HPLC
  4. customto give

Sources & evidence

ORD record
ord-9412ffff46134f78ae3acde122fb6a7d
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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