Hydrochloric Acid → HCID 20672402, compound

HRID 1386732Notes

Reaction equation

HRID 1386732 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1([CH2:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.Cl.[CH:27]([C@@H:29]1[C@@H:33]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:32][N:31]([C@H:40]([CH:53]2[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]2)[C:41]([O:43]CC2C=CC(OC)=CC=2)=[O:42])[CH2:30]1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:10][C:11]1([CH2:17][CH2:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:16][CH2:15][N:14]([CH2:27][C@@H:29]2[C@@H:33]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:32][N:31]([C@H:40]([CH:53]3[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]3)[C:41]([OH:43])=[O:42])[CH2:30]2)[CH2:13][CH2:12]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 21180755HCID 21180755, compoundHCID 53654320alpha-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester

Product 1

HCID 20672402HCID 20672402, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

To a solution of DIEA (0.019 mL, 0.11 mmol) in 0.5 mL of 1,2-dichloroethane was added 4fluoro-4-(3-phenylpropyl) piperidine.HCl (21 mg, 0.08 mmol) To this solution, a solution of 2-(R)-((3-(R)-formyl)-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid, (4-methoxy) benzyl ester (25 mg, 0.052 mmol, from EXAMPLE 33, Step E) was added. A slurry of sodium triacetoxyborohydride (35 mg, 0.17 mmol) in 0.5 mL of 1,2-dichloroethane was then added. The reaction mixture was allowed to stand at rt for 16 hours. The solvent was removed and the product was purified by preprative HPLC (column: YMC Combiprep ODS-A 20×50 mm, gradient: 10% acetonitrile/H2O w/0.1% TFA for 1.5 min then ramp to 90% acetonitrile/H2O w/0.1% TFA over 7.5 min, flow: 20 mL/min). The isolated material was stirred in 3 mL formic acid for 16 h. After removal of solvent, the residue was purified by ion exchange chromatography (0.5 grams Varian SCX resin, 100% MeOH→2.0 M NH3/MeOH) to give 13 mg (48%) of the title compound: 1H NMR (400 MHz, CD3OD) δ 1.15-1.37 (m, 4H), 1.41-1.59 (m, 5H), 1.62-1.69 (m, 5H), 1.72-1.91 (m, 5H), 2.04 (t, J=10, 1H), 2.24 (t, J=11, 1H), 2.32 (dd, J=4.5, 13, 1H), 2.46 (dd, J=10, 13 Hz, 2H), 2.58 (t, J=7.5 Hz, 2H), 2.62-2.65 (m, 1H), 2.77 (m, 1H), 3.16 (dd, J=11, 19, 1H), 3.45 (m, 2H), 3.51 (d, J=3.9, 1H), 3.58-3.64 (m, 2H), 7.12-7.16 (m, 3H), 7.22-7.29 (m, 3H), 7.33-7.37 (m, 4H); ESI-MS: 521 (M+H); HPLC A: 2.65 min.

Workup

  1. customThe solvent was removed
  2. customthe product was purified by preprative HPLC (column
  3. customfor 1.5 min
  4. customover 7.5 min
  5. customAfter removal of solvent
  6. customthe residue was purified by ion exchange chromatography (0.5 grams Varian SCX resin, 100% MeOH→2.0 M NH3/MeOH)

Sources & evidence

ORD record
ord-d5eb066242b44203b69f8815785a413c
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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