Hydrochloric Acid → MLN4924 hydrochloride

HRID 715632Notes

Reaction equation

HRID 715632 reaction equation
[S:1](=[O:31])(=[O:30])([O:3][CH2:4][C@@H:5]1[CH2:9][C@@H:8]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH:19][C@@H:20]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH2:22][CH2:21]4)[C:13]=3[CH:12]=[CH:11]2)[CH2:7][C@@H:6]1[OH:29])[NH2:2].[ClH:32]>C(O)C>[ClH:32].[S:1](=[O:31])(=[O:30])([O:3][CH2:4][C@@H:5]1[CH2:9][C@@H:8]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH:19][C@@H:20]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH2:22][CH2:21]4)[C:13]=3[CH:12]=[CH:11]2)[CH2:7][C@@H:6]1[OH:29])[NH2:2]

Participants

4

Reactant 2

HCID 313Hydrochloric Acid2×HCID 16720766Pevonedistat

Product 1

HCID 66576990MLN4924 hydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
72.5 °C

Procedure

A flask was charged with ((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate (25 g, 56.4 mmol) and 200-proof ethanol (300 mL). The mixture was heated to 70-75° C. to afford a clear solution. The mixture was cooled to 50±5° C. 1.25M hydrogen chloride in ethanol (25 mL, 31 mmol) was added rapidly at a rate to maintain a temperature of 50±5° C. The mixture was then seeded with Form 1. Further 1.25M HCl (25 mL, 31 mmol) was added over a period of about 60 minutes, maintaining a temperature of 50±5° C. The mixture was then stirred at 50±5° C. for about 2 hours. The mixture was then cooled to 20±5° C. over about 2 hours and then stirred for about 17 hours. The solid product was then isolated by filtration and washed with 200-proof ethanol (50 mL). The solids were dried by aspiration on the filter for about 5 hours, and then further dried under reduced pressure at 30-35° C. to afford the title compound (22.5 g) as a white solid.

Workup

  1. customto afford a clear solution
  2. temperatureThe mixture was cooled to 50±5° C
  3. temperatureto maintain a temperature of 50±5° C
  4. temperaturemaintaining a temperature of 50±5° C
  5. temperatureThe mixture was then cooled to 20±5° C. over about 2 hours
  6. stirringstirred for about 17 hours
  7. customThe solid product was then isolated by filtration
  8. washwashed with 200-proof ethanol (50 mL)
  9. customThe solids were dried by aspiration on the
  10. filtrationfilter for about 5 hours
  11. customfurther dried under reduced pressure at 30-35° C.

Sources & evidence

ORD record
ord-e780e32940a64d63a0ab8a7c17926388
Source dataset
uspto-grants-2015_11
Patent number
US09187482B2

Reaction notes

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