Hydrochloric Acid → Hydrochloric Acid

HRID 1091992Notes

Reaction equation

HRID 1091992 reaction equation
[C:1]([N:5]1[CH2:9][C@@H:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[C@H:7]([C:18]([N:20]2[CH2:25][CH2:24][CH:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[C@@H:33]([NH:35][C:36](=[O:38])[CH3:37])[CH3:34])[CH2:22][CH2:21]2)=[O:19])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].Cl.[C:40]([O:43][CH:44]([CH3:46])[CH3:45])(=[O:42])[CH3:41]>C(O)(C)C>[ClH:32].[CH3:45][CH:44]([OH:43])[CH3:46].[C:40]([O:43][CH:44]([CH3:46])[CH3:45])(=[O:42])[CH3:41].[C:1]([N:5]1[CH2:9][C@@H:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[C@H:7]([C:18]([N:20]2[CH2:25][CH2:24][CH:23]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[C@@H:33]([NH:35][C:36](=[O:38])[CH3:37])[CH3:34])[CH2:22][CH2:21]2)=[O:19])[CH2:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 3

HCID 313Hydrochloric Acid3×HCID 7915Isopropyl AcetateHCID 11642422MK-0493 free base2×

Product 3

HCID 313Hydrochloric AcidHCID 11642422MK-0493 free baseHCID 223498672-Propanol isopropyl acetate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Conditions

Temperature
35 °C

Procedure

Method To a 50 mL flask was added a solution of the free base (1-3) of Compound I in isopropyl acetate (13.9 mL at 160 g/L). The solution was heated to 35° C., and HCl in isopropyl alcohol (1.33 N, 6.1 mL, 1 eq) was added in one portion. The resulting solution was heated to 60° C. and a second equivalent of 1.33N HCl in isopropyl alcohol (6.1 mL) was added in one portion. To the resulting solution at 60° C. was added seed of the bis HCl Form II of Compound I (25.2 mg). After seeding, the mixture was cooled to 20 C. over at least 1 hour, and then aged at 20° C. for a minimum of 12 hours. The mixture was filtered, and washed with isopropyl acetate (5.6 mL) to give the bis HCl salt Form II 2-propanol/isopropyl acetate co-solvate of compound I (1-9).

Workup

  1. temperatureThe resulting solution was heated to 60° C.
  2. temperaturethe mixture was cooled to 20 C
  3. waitover at least 1 hour
  4. customaged at 20° C. for a minimum of 12 hours
  5. filtrationThe mixture was filtered
  6. washwashed with isopropyl acetate (5.6 mL)

Sources & evidence

ORD record
ord-5e96721248734521ab8ed08ff016db3c
Source dataset
uspto-grants-2012_03
Patent number
US08129413B2

Reaction notes

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