Tert-Butylamine → HCID 178449075, compound

HRID 2068523Notes

Reaction equation

HRID 2068523 reaction equation
O.[F:2][C:3]([F:46])([F:45])[C:4]1[CH:5]=[C:6]([CH2:14][N:15]([C:39]2[N:40]=[N:41][N:42]([CH3:44])[N:43]=2)[C@@H:16]2[C:22]3[CH:23]=[C:24]([CH3:28])[CH:25]=[C:26]([CH3:27])[C:21]=3[N:20]([CH2:29][C@H:30]3[CH2:35][CH2:34][C@H:33]([C:36]([OH:38])=[O:37])[CH2:32][CH2:31]3)[CH2:19][CH2:18][CH2:17]2)[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1.[C:47]([NH2:51])([CH3:50])([CH3:49])[CH3:48]>CCCCCCC.C(O)(C)C>[CH:36]([OH:38])([CH3:33])[CH3:47].[C:47]([NH2:51])([CH3:50])([CH3:49])[CH3:48].[F:13][C:10]([F:11])([F:12])[C:8]1[CH:7]=[C:6]([CH2:14][N:15]([C:39]2[N:40]=[N:41][N:42]([CH3:44])[N:43]=2)[C@@H:16]2[C:22]3[CH:23]=[C:24]([CH3:28])[CH:25]=[C:26]([CH3:27])[C:21]=3[N:20]([CH2:29][C@H:30]3[CH2:35][CH2:34][C@H:33]([C:36]([OH:38])=[O:37])[CH2:32][CH2:31]3)[CH2:19][CH2:18][CH2:17]2)[CH:5]=[C:4]([C:3]([F:2])([F:46])[F:45])[CH:9]=1

Participants

5

Reactant 2

HCID 6385Tert-ButylamineHCID 178423621HCID 178423621, compound

Product 1

HCID 178449075HCID 178449075, compound

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8900HeptaneSolvent

Conditions

Temperature
69.0999984741211 °C

Procedure

Set up a 1 L three neck round bottom flask fitted with a mechanical stirrer, temperature controller, addition funnel, and heating mantle. Suspend Trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl](2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid hydrate (50 g) in heptane (500 mL). Heat the slurry to 69.1° C. and add tert-butylamine (5.57 g) as a solution in isopropyl alcohol (70 mL) and rinse in with 5 mL additional isopropyl alcohol. A solution forms immediately upon addition. During addition, temperature drops to 63° C. but heats back up to 69° C. once addition is complete. Seed with a spatula tip of Trans-4-[[(5S)-5-[[[3,5-bis(trifluoromethyl)phenyl]methyl](2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-7,9-dimethyl-1H-1-benzazepin-1-yl]methyl]-cyclohexanecarboxylic acid tert-butylamine. A suspension begins to form—continue stirring at 69° C. Begin cooling the reaction to 55° C. In about an hour, a thick slurry forms. Continue cooling to 45° C. In about an hour, bring temperature of slurry down to 35° C. In about 2 hours, remove heat source and allow to cool to ambient temperature. In about 3 hours, filter the slurry (temperature is now 21° C.) and rinse with 100 mL of heptane. Dry using a vacuum for about an 1.5 hours. Dry over the weekend in vacuo at 33° C. This results in 55.9 g. The XRD spectrum was collected as described in Example 7. Table 4 below lists the peaks obtained from the XRD spectrum.

Workup

  1. customfitted with a mechanical stirrer
  2. additiontemperature controller, addition funnel
  3. temperatureheating mantle
  4. washrinse in with 5 mL additional isopropyl alcohol
  5. additionA solution forms immediately upon addition
  6. additionDuring addition, temperature drops to 63° C.
  7. customheats back up to 69° C.
  8. additiononce addition
  9. temperatureBegin cooling
  10. customthe reaction to 55° C
  11. waitIn about an hour
  12. temperatureContinue cooling to 45° C
  13. waitIn about an hour
  14. customdown to 35° C
  15. customremove
  16. temperatureheat source
  17. temperatureto cool to ambient temperature
  18. waitIn about 3 hours
  19. filtrationfilter the slurry (temperature
  20. customis now 21° C.
  21. washrinse with 100 mL of heptane
  22. customDry
  23. customfor about an 1.5 hours
  24. customDry over the weekend in vacuo at 33° C
  25. customThis results in 55.9 g
  26. customThe XRD spectrum was collected
  27. customTable 4 below lists the peaks obtained from the XRD spectrum

Sources & evidence

ORD record
ord-dfebf3e0d6524a1280ba291795d847b8
Source dataset
uspto-grants-2012_10
Patent number
US08299060B2

Reaction notes

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