Hydrochloric Acid → HCID 57388936, compound

HRID 2407000Notes

Reaction equation

HRID 2407000 reaction equation
C([O:3][C:4](=[O:38])[CH2:5][CH2:6][NH:7][C:8]([C:10]1[CH:11]=[N:12][C:13]([NH:16][C@H:17]([C:22]2[CH:23]=[N:24][C:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=3)=[N:26][CH:27]=2)[CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:14][CH:15]=1)=[O:9])C.C(OCC)(=O)C.[OH-].[Na+].Cl>O1CCCC1.CO>[CH3:20][CH:19]([CH3:21])[CH2:18][C@H:17]([NH:16][C:13]1[N:12]=[CH:11][C:10]([C:8]([NH:7][CH2:6][CH2:5][C:4]([OH:38])=[O:3])=[O:9])=[CH:15][CH:14]=1)[C:22]1[CH:23]=[N:24][C:25]([C:28]2[CH:29]=[CH:30][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:32][CH:33]=2)=[N:26][CH:27]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl Acetate2×HCID 14798Sodium HydroxideHCID 67980859HCID 67980859, compound

Product 1

HCID 57388936HCID 57388936, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

3-[(6-{(S)-3-Methyl-1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-butylamino}-pyridine-3-carbonyl)-amino]-propionic acid ethyl ester (29.2 g wet with ethyl acetate, theoretically 54.0 mmol) was dissolved in tetrahydrofuran (135 mL) and methanol (45 mL), and 1.0 M sodium hydroxide (135 mL) was added. This was stirred at room temperature for 20 min before most of the organics were rotovapped off. A small amount of tetrahydrofuran was added and the mostly aqueous contents were stirred in an ice bath. 1 N HCl (130 mL) was added until pH 5. Ethyl acetate was added and stirred for ˜20 min to ensure constant pH. The material was added to a sep funnel and the layers separated. The aqueous was back extracted with additional ethyl acetate and the combined organics were washed with brine and dried over MgSO4. This was concentrated and the solid was placed in a vacuum oven for two days to give 3-[(6-{(S)-3-methyl-1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-butylamino}-pyridine-3-carbonyl)-amino]-propionic acid as a white foam. 1H NMR (400 MHz, DMSO-d6, δ): 12.16 (s, 1 H) 8.97 (s, 2 H) 8.54 (d, J=8.2 Hz, 2 H) 8.41 (d, J=2.0 Hz, 1 H) 8.19 (t, J=5.4 Hz, 1 H) 7.87 (d, J=8.4 Hz, 2 H) 7.78 (dd, J=8.8, 2.3 Hz, 1 H) 7.68 (d, J=8.0 Hz, 1 H) 6.58 (d, J=8.6 Hz, 1 H) 5.09-5.26 (m, 1 H) 3.38 (q, J=6.7 Hz, 2 H) 2.44 (t, J=7.0 Hz, 2 H) 1.80-1.94 (m, 1 H) 1.57-1.77 (m, 2 H) 0.96 (d, J=6.1 Hz, 3 H) 0.92 (d, J=6.3 Hz, 3 H); MS (M+1): 502.3.

Workup

  1. stirringthe mostly aqueous contents were stirred in an ice bath
  2. stirringstirred for ˜20 min
  3. additionThe material was added to a sep funnel
  4. customthe layers separated
  5. extractionThe aqueous was back extracted with additional ethyl acetate
  6. washthe combined organics were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationThis was concentrated
  9. waitthe solid was placed in a vacuum oven for two days

Sources & evidence

ORD record
ord-e39f432953d9460db9386042778a7c2f
Source dataset
uspto-grants-2014_08
Patent number
US08809342B2

Reaction notes

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