Hydrochloric Acid → HCID 10163761, compound

HRID 432108Notes

Reaction equation

HRID 432108 reaction equation
CC([Si](C)(C)[O:6][C@H:7]([C:51]1[CH:52]=[N:53][CH:54]=[CH:55][CH:56]=1)[CH2:8][N:9]([CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:43]=[CH:42][C:31]([C:32]([O:34]CC4C=CC=CC=4)=[O:33])=[C:30]([O:44][C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[CH:29]=3)[CH:24]=2)[O:19]1)C(OC(C)(C)C)=O)(C)C.Cl>C(O)C.O1CCOCC1.[Pd]>[OH:6][C@H:7]([C:51]1[CH:52]=[N:53][CH:54]=[CH:55][CH:56]=1)[CH2:8][NH:9][CH2:17][C@H:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:28]3[CH:43]=[CH:42][C:31]([C:32]([OH:34])=[O:33])=[C:30]([O:44][C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)[CH:29]=3)[CH:24]=2)[O:19]1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 59118138HCID 59118138, compound

Product 1

HCID 10163761HCID 10163761, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Phenylmethyl 4-{(2R)-2-[([(2R)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2-(3-pyridinyl)ethyl]{[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]-3,4-dihydro-2H-chromen-6-yl}-2-(phenyloxy)benzoate (Example 191, 69 mg, 0.086 mmol) was stirred over a suspension of 10% Pd/C (7 mg) in ethanol (5 mL) under a hydrogen atmosphere for 15 hours. Solids were removed by filtration through Celite®, and the filtrate was concentrated in vacuo. The carboxylic acid intermediate was collected as a colorless oil (25 mg, 41%): 1H NMR (300 MHz, CD3OD) δ 8.66-8.58 (m, 2H), 7.99 (d, 1H), 7.92 (d, 1H), 7.58-7.54 (m, 2H), 7.51-7.41 (m, 2H), 7.37-7.34 (m, 2H), 7.21-7.16 (m, 2H), 7.10 (d, 2H), 6.86 (d, 1H), 5.27-5.15 (m, 1H), 4.38-4.31 (m, 1H), 3.86-3.54 (m, 4H), 2.96-2.90 (m, 2H), 2.13-2.00 (m, 1H), 1.87-1.75 (m, 1H), 1.56 (d, 9H), 1.00 (s, 9H), 0.18 (d, 3H), 0.00 (s, 3H). The carboxylic acid intermediate (25 mg, 0.04 mmol) was stirred in an excess of 4M HCl in dioxane at room temperature for 18 hours. The volatile components were removed by rotary evaporation, and the residue was washed with dichloromethane. After drying under vacuum, the title compound was collected as the di-hydrochloride salt (16 mg, 80%): 1H NMR (300 MHz, CD3OD) δ 9.04 (broad s, 1H), 8.89 (broad s, 1H), 8.77 (d, 1H), 8.15 (t, 1H), 8.00 (d, 1H), 7.46 (d, 1H), 7.38-7.33 (m, 4H), 7.14-7.08 (m, 2H), 6.98 (d, 3H), 5.45 (d, 1H), 4.50 (t, 1H), 3.76-3.55 (m, 5H), 3.52-3.35 (m, 2H), 2.99-2.85 (m, 2H), 2.18-2.11 (m, 1H), 1.85-1.75 (m, 1H); MS m/z 497.2 (MH+ of the free base).

Workup

  1. customSolids were removed by filtration through Celite®
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe carboxylic acid intermediate was collected as a colorless oil (25 mg, 41%)
  4. customThe volatile components were removed by rotary evaporation
  5. washthe residue was washed with dichloromethane
  6. customAfter drying under vacuum
  7. customthe title compound was collected as the di-hydrochloride salt (16 mg, 80%)

Sources & evidence

ORD record
ord-6119ee982bad4075881e581ab678ddb8
Source dataset
uspto-grants-2003_12
Patent number
US06660752B2

Reaction notes

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