Diisopropylethylamine → HCID 59278243, compound

HRID 559780Notes

Reaction equation

HRID 559780 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[N:14][CH:15]=[C:16]([C:17]([OH:19])=O)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.[CH3:52][S:53]([C:56]1[N:61]=[CH:60][C:59]([C@@H:62]([NH2:65])[CH2:63][CH3:64])=[CH:58][CH:57]=1)(=[O:55])=[O:54].C(=O)(O)[O-].[Na+]>CN(C=O)C.O>[CH3:52][S:53]([C:56]1[N:61]=[CH:60][C:59]([C@@H:62]([NH:65][C:17]([C:16]2[C:11]3[CH:10]=[N:9][N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[C:12]=3[CH:13]=[N:14][CH:15]=2)=[O:19])[CH2:63][CH3:64])=[CH:58][CH:57]=1)(=[O:55])=[O:54]

Participants

8

Reactant 5

HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 592781371-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acidHCID 66727435HCID 66727435, compound

Product 1

HCID 59278243HCID 59278243, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (37.8 g, 146.9 mmol) in DMF (400 mL) was added DIPEA (50 mL, 287.0 mmol) followed by TBTU (49.5 g, 154.1 mmol). The mixture stirred for 1 hour, to afford a precipitate. To the mixture was added (S)-1-(6-methanesulfonyl-pyridin-3-yl)-propylamine hydrochloride (32.0 g, 127.6 mmol) followed by DIPEA (30 mL, 172.2 mmol). The mixture stirred overnight and was then poured into water (2.5 L) with sodium bicarbonate (50 g) added. The solid was collected by filtration washing with aqueous sodium carbonate (2 L) and then water (3 L). The solid was dried by pulling vacuum through the filter cake. The crude material was dissolved in dichloromethane and passed through a pad of silica gel (2000 mL funnel) using ethyl acetate-dichloromethane (1:9, then 2:8, then 100:0). The material from the pad was triturated with ether and the solid was collected by filtration. The solid was then dissolved in hot acetonitrile (1 L) and diluted with water (1 L). The product crystallized from the light yellow solution upon cooling overnight. The solid was collected by filtration washing with a 1:1 mixture of acetonitrile-water and then dried by pulling vacuum through the filter cake for 4 hours and then at 90° C. under house vacuum for approximately 11 hours (until a constant weight) to afford the title compound as a crystalline solid.

Workup

  1. customto afford a precipitate
  2. stirringThe mixture stirred overnight
  3. additionadded
  4. filtrationThe solid was collected by filtration
  5. washwashing with aqueous sodium carbonate (2 L)
  6. customThe solid was dried
  7. dissolutionThe crude material was dissolved in dichloromethane
  8. customThe material from the pad was triturated with ether
  9. filtrationthe solid was collected by filtration
  10. dissolutionThe solid was then dissolved in hot acetonitrile (1 L)
  11. additiondiluted with water (1 L)
  12. customThe product crystallized from the light yellow solution
  13. temperatureupon cooling overnight
  14. filtrationThe solid was collected by filtration
  15. washwashing with a 1:1 mixture of acetonitrile-water
  16. customdried
  17. customfor 4 hours

Sources & evidence

ORD record
ord-ac37b5efa555457682dc42af33166a2f
Source dataset
uspto-grants-2011_11
Patent number
US08063065B2

Reaction notes

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