Hydrochloric Acid → HCID 68463096, compound

HRID 474205Notes

Reaction equation

HRID 474205 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C:14]3[CH:15]=[N:16][C:17]([O:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)=[CH:18][CH:19]=3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[ClH:28]>C(O)C.CCOCC.CCOCC>[OH2:13].[ClH:28].[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C:14]3[CH:15]=[N:16][C:17]([O:20][C:21]4[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=4)=[CH:18][CH:19]=3)=[O:13])[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 24771368JNJ-39220675

Product 1

HCID 68463096HCID 68463096, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21585056Diethyl ether ethanolSolvent

Conditions

Temperature
5 °C

Procedure

A 3-L, 3-necked, round-bottomed flask was equipped with a mechanical stirrer, addition funnel and a thermocouple. The flask was charged with a solution of crude (4-cyclobutyl-[1,4]diazepan-1-yl)-[6-(4-fluoro-phenoxy)-pyridin-3-yl]methanone (118.0 g, 319.8 mmol) in ethanol/Et2O (1:1, 800 mL). The reaction vessel was cooled to ca. 5° C. in an ice-water bath. HCl (2 M in Et2O, 152 mL, 304 mmol, 0.95 equiv.) was added drop-wise via the addition funnel over 30 min. The resulting suspension was stirred for 2 h, and then diluted with Et2O (200 mL). The resulting suspension was stirred at rt for 16 h. The suspension was re-cooled to 0° C., maintained at that temperature for 2 h with agitation, then filtered. The filter-cake was broken and washed with Et2O/EtOH (60:40, 100 mL×3) and the product dried under house vacuum for 1 h, then in a vacuum oven at 50° C. for 48 h. The product (113.5 g) was suspended in Et2O (2 L) and agitated (mechanical stirrer) for 6 h. The suspension was filtered, the filter-cake broken and washed with Et2O (3×100 mL). The product was dried in a vacuum oven at 45° C. for 16 h (106.8 g, 82%). 1H NMR (400 MHz, D2O) δ ppm: 8.09-8.05 (m, 1H), 7.88-7.81 (m, 1H), 7.13-7.09 (m, 4H), 7.02 (d, J=8.64 Hz, 1H), 4.15-4.10 (m, 1H), 3.87-3.39 (m, 6H), 3.07-2.90 (m, 2H), 2.28-1.99 (m, 6H), 1.75-1.63 (m, 2H). MS m/z (ESI+): 370.1 (M+H+). HPLC (Method B): Rt=7.13 min. Anal. calcd for C21H24FN3O2.HCl.H2O (monohydrochloride-monohydrate): C, 59.50; H, 6.42; N, 9.91. Found: C, 59.36; H, 6.66; N, 9.98.

Workup

  1. stirringThe resulting suspension was stirred at rt for 16 h
  2. temperatureThe suspension was re-cooled to 0° C.
  3. temperaturemaintained at that temperature for 2 h with agitation
  4. filtrationfiltered
  5. washwashed with Et2O/EtOH (60:40, 100 mL×3)
  6. customthe product dried under house vacuum for 1 h
  7. waitin a vacuum oven at 50° C. for 48 h
  8. stirringagitated (mechanical stirrer) for 6 h
  9. filtrationThe suspension was filtered
  10. washwashed with Et2O (3×100 mL)
  11. customThe product was dried in a vacuum oven at 45° C. for 16 h (106.8 g, 82%)

Sources & evidence

ORD record
ord-1653d69d189940c59c6dbf8160f2df4a
Source dataset
uspto-grants-2014_01
Patent number
US08637520B2

Reaction notes

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