Hydrochloric Acid → HCID 131734439, compound

HRID 588739Notes

Reaction equation

HRID 588739 reaction equation
Cl.[CH3:2][CH:3]1[N:8]([CH2:9][C:10]([F:13])([F:12])[F:11])[C:7](=[O:14])[CH:6]([CH2:15][CH:16]=[CH:17][C:18]2[CH:19]=[C:20]3[CH2:43][C@@:25]4([C:33]5[C:28](=[N:29][CH:30]=[CH:31][CH:32]=5)[N:27](COCC[Si](C)(C)C)[C:26]4=[O:42])[CH2:24][C:21]3=[N:22][CH:23]=2)[CH2:5][CH:4]1[C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[C:46]([F:51])[C:45]=1[F:52].[OH-].[NH4+]>CO>[CH3:2][CH:3]1[N:8]([CH2:9][C:10]([F:12])([F:11])[F:13])[C:7](=[O:14])[C@@H:6]([CH2:15][CH:16]=[CH:17][C:18]2[CH:19]=[C:20]3[CH2:43][C:25]4([C:33]5[C:28](=[N:29][CH:30]=[CH:31][CH:32]=5)[NH:27][C:26]4=[O:42])[CH2:24][C:21]3=[N:22][CH:23]=2)[CH2:5][CH:4]1[C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[C:46]([F:51])[C:45]=1[F:52]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 131734440HCID 131734440, compound

Product 1

HCID 131734439HCID 131734439, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

HCl gas was bubbled into a solution of (3′S)-3-(3-(6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl)prop-1-en-1-yl)-1′-((2-(trimethylsilyl)ethoxy)methyl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (0.091 g, 0.125 mmol) in MeOH (5 mL) cooled to 0° C. until saturated. The resulting mixture was stirred at 0° C. for 1 h and then concentrated to dryness in vacuo. To a solution of this crude mixture in MeOH (5 mL) was added ammonium hydroxide (0.27 mL, 1.99 mmol), and the reaction was stirred at ambient temperature for 30 min. The reaction was concentrated to dryness in vacuo. The crude product was purified by reverse-phase HPLC, eluting with 5% acetonitrile in water (0.1% TFA used as a modifier) initially, grading to 85% acetonitrile in water, to give the title compound as a mixture of ca. 1 major and 2 minor compounds (pairs of enantiomers). MS: m/z=601.2 (M+1). Major diastereoisomer: 1H NMR (500 MHz, CDCl3) δ 8.51 (s, 1H), 8.15 (dd, 1H, J=5.7, 1.4 Hz), 7.90 (s, 1H), 7.42 (dd, 1H, J=7.4, 1.4 Hz), 7.06 (dd, 1H, J=7.4, 5.7 Hz), 6.94-6.90 (m, 1H), 6.72-6.70 (m, 1H), 6.49-6.46 (m, 1H), 4.90-4.78 (m, 1H), 4.00-3.90 (m, 2H), 3.90-3.75 (m, 2H), 3.75-3.60 (m, 1H), 3.55 (d, 1H, J=17.5 Hz), 3.40-3.20 (m, 2H), 2.92-2.80 (m, 2H), 2.78-2.68 (m, 1H), 2.55 (dt, 1H, J=13.7, 4.1 Hz), 1.86 (bd, 1H, J=13.7 Hz), 1.08 (d, 3H, J=6.6 Hz).

Workup

  1. concentrationconcentrated to dryness in vacuo
  2. stirringthe reaction was stirred at ambient temperature for 30 min
  3. concentrationThe reaction was concentrated to dryness in vacuo
  4. customThe crude product was purified by reverse-phase HPLC
  5. washeluting with 5% acetonitrile in water (0.1% TFA

Sources & evidence

ORD record
ord-38b66d4127fe47c4a1b60aff5816c68d
Source dataset
uspto-grants-2016_01
Patent number
US09227972B2

Reaction notes

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