Sodium triacetoxyborohydride → HCID 20672399, compound

HRID 1386719Notes

Reaction equation

HRID 1386719 reaction equation
[CH:1]([C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][N:5]([C@H:14]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:15]([O:17]CC2C=CC(OC)=CC=2)=[O:16])[CH2:4]1)=O.[N:33]1[N:34]=[N:35][N:36]2[C:41]([CH2:42][CH2:43][CH2:44]N3CCCCC3)=[CH:40][CH:39]=[CH:38][C:37]=12.C(O[BH-](O[C:61](=O)[CH3:62])OC(=O)C)(=O)C.[Na+]>ClCCCl>[N:33]1[N:34]=[N:35][N:36]2[C:41]([CH2:42][CH2:43][CH2:44][CH:62]3[CH2:61][CH2:6][N:5]([CH2:1][C@@H:3]4[C@@H:7]([C:8]5[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=5)[CH2:6][N:5]([C@H:14]([CH:27]5[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]5)[C:15]([OH:17])=[O:16])[CH2:4]4)[CH2:4][CH2:3]3)=[CH:40][CH:39]=[CH:38][C:37]=12

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 21180649HCID 21180649, compound2×HCID 53654320alpha-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester

Product 1

HCID 20672399HCID 20672399, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 2-(R)-(3-(R)formyl-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid, (4-methoxy)benzyl ester (33 mg, 0.075 mmol, from EXAMPLE 33, Step E), 3-(tetrazolo[4,5-a]pyridin-5-yl)propylpiperidine.HCl (27 mg, 0.097 mmol from EXAMPLE 34, Step B) sodium triacetoxyborohydride, 32 mg (0.15 mmol) and TEA (0.014 mL, 0.097 mmol), in 1.0 mL 1,2-dichloroethane was stirred overnight. The solvent was removed and the product was purified by preprative HPLC (column: YMC Combiprep ODS-A 20×50 mm, gradient: 5% acetonitrile/H2O w/ 0.1% TFA for 1 min then ramp to 100% acetonitrile/H2O w/ 0.1% TFA over 6 min, flow: 20 mL/min). The material was stirred in 3 mL formic acid for 8 h. After removal of solvent the purification was accomplished by preprative HPLC (column: YMC Combiprep ODS-A 20×50 mm, gradient: 5% acetonitrile/H2O w/ 0.1% TFA for 1 min then ramp to 100% acetonitrile/H2O w/0.1% TFA over 6 min, flow: 20 mL/min) to give 11 mg (27%) of the title compound: 1H NMR (500 MHz) δ 1.02-1.98 (22H), 2.05-2.1 (m, 1H), 2.1-2.2 (m, 1H), 2.3-2.4 (m, 1H), 2.6-3.4 (8H), 3.8-3.9 (t, 2H), 4.51-4.55 (m, 1H), 7.2-7.33 (m, 5H), 7.48-7.49 (d, 1H, J=9 Hz), 7.94-7.96 (d, 1H, J=9 Hz): ESI-MS, M/z; (M+H)=545.5 (obs), 545.3 (calc.).

Workup

  1. customThe solvent was removed
  2. customthe product was purified by preprative HPLC (column
  3. customfor 1 min
  4. customover 6 min
  5. customAfter removal of solvent
  6. customthe purification
  7. customfor 1 min
  8. customover 6 min

Sources & evidence

ORD record
ord-d565735cba974452a95feb2031a0194c
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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