Hydrochloric Acid → HCID 12003961, compound

HRID 2245870Notes

Reaction equation

HRID 2245870 reaction equation
C([O:3][C:4](=[O:46])[CH2:5][CH2:6][N:7]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:45])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C@@H:21]([N:29]3[CH2:34][C@@H:33]([CH3:35])[N:32]([CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[CH:38]=4)[CH2:31][C@@H:30]3[CH3:44])[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=3)[CH:16]=2)[CH2:9][CH2:8]1)C.[OH-].[Na+].Cl>C1COCC1>[F:43][C:39]1[CH:38]=[C:37]([CH:42]=[CH:41][CH:40]=1)[CH2:36][N:32]1[C@H:33]([CH3:35])[CH2:34][N:29]([C@@H:21]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=2)[C:17]2[CH:16]=[C:15]([CH:20]=[CH:19][CH:18]=2)[C:14]([N:10]2[CH2:11][CH2:12][CH2:13][N:7]([CH2:6][CH2:5][C:4]([OH:46])=[O:3])[CH2:8][CH2:9]2)=[O:45])[C@@H:30]([CH3:44])[CH2:31]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 12003960HCID 12003960, compound

Product 1

HCID 12003961HCID 12003961, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The mixture of 3-(4-{3-[(R)-[(2S,5R)-4-(3-Fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-(3-hydroxy-phenyl)-methyl]-benzoyl}-[1,4]diazepan-1-yl)-propionic acid ethyl ester (800 mg, Example 14), THF (10 mL) and 1 N NaOH solution (6 mL) was stirred at room temperature for overnight. The reaction solution was neutralized by the addition of 1 N HCl solution (6 mL). The mixture was dried under rotary evaporator. For the complete removal of water, CH3OH (25 mL) was added to the flask containing the desired product and the resulting solution was dried by rotary evaporator. The process of adding CH3OH and drying CH3OH was repeated one more time. Ethanol (20 mL) was added to the residual remained in the flask. Solid (NaCl) was seen in the ethanol solution. The mixture was filtered thru a fritted filter. The solid was resined by ethanol (15 mL). The filtrate was concentrated to give crude product, which was purified by reverse phase C-18 column chromatography conducted on CombiFlash™ Sq 16× (gradient: 100% water to 100% methanol) to give 3-(4-{3-[(R)-[(2S,5R)-4-(3-fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-(3-hydroxy-phenyl)-methyl]-benzoyl}-[1,4]diazepan-1-yl)-propionic acid (320 mg; 42%). 1H NMR (300 MHz, CD3OD) δ 7.61 (m, 1H), 7.50-7.39 (m, 2H), 7.32 (m, 2H), 7.20-7.08 (m, 3H), 6.98 (m, 1H), 6.73 (m, 3H), 5.16 (s, 1H), 3.99-3.92 (m, 2H), 3.60 (bs, 1H), 3.50 (m, 2H), 3.35 (m, 2H), 3.23 (m, 3H), 3.08 (m, 1H), 2.99 (m, 1H), 2.75-2.66 (m, 4H), 2.54 (m, 1H), 2.46 (m, 1H), 2.17-1.99 (m, 4H), 1.13 (m, 6H).

Workup

  1. customThe mixture was dried under rotary evaporator
  2. customFor the complete removal of water, CH3OH (25 mL)
  3. additionwas added to the flask
  4. additioncontaining the desired product
  5. customthe resulting solution was dried by rotary evaporator
  6. dry with materialThe process of adding CH3OH and drying CH3OH
  7. additionEthanol (20 mL) was added to the residual
  8. filtrationThe mixture was filtered
  9. concentrationThe filtrate was concentrated
  10. customto give crude product, which
  11. customwas purified by reverse phase C-18 column chromatography

Sources & evidence

ORD record
ord-e36d54460d6d445ea5208ac2947acebb
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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