Hydrochloric Acid → HCID 86687469, compound

HRID 1473419Notes

Reaction equation

HRID 1473419 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br:18][C:19]1[C:28]2[C:23](=[CH:24][C:25]([S:29](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:31])=[O:30])=[CH:26][CH:27]=2)[CH:22]=[N:21][CH:20]=1.NC1N=CC=CN=1.[ClH:51]>C1COCC1.CO.C(O)(=O)C>[ClH:51].[Br:18][C:19]1[C:28]2[C:23](=[CH:24][C:25]([S:29]([NH:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][N:3]=3)(=[O:31])=[O:30])=[CH:26][CH:27]=2)[CH:22]=[N:21][CH:20]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 79782-AminopyrimidineHCID 689584-AminopyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 86687467HCID 86687467, compound

Product 2

HCID 313Hydrochloric AcidYield 3%HCID 86687469HCID 86687469, compoundYield 24.29%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a flask containing ice cold suspension of pyrimidin-4-amine (0.402 g, 4.23 mmol) in THF (5.42 ml) was added lithium bis(trimethylsilyl)amide (1M in THF) (1.550 ml, 1.550 mmol) drop wise over 10 min. The mixture was stirred for 15 min providing a white suspension. A solution of perfluorophenyl 4-bromoisoquinoline-7-sulfonate (0.640 g, 1.409 mmol) in THF (5.0 ml) was added drop wise and the resulting mixture stirred for 1 hr. To the solution was added acetic acid (500 μl) and the solution dried under reduced pressure. The crude material was purified with a 40 g HP Silicycle column (SiliCycle, Inc. Quebec City, Canada) ramping EtOAc in heptane (0 to 25%) to elute starting material, then MeOH in DCM (0 to 20%) providing product which had coeluted with aminopyrimidine. The mixture was purified with a 10 g PE-AX column (Biotage AB, Uppsala, Sweden) washing with MeOH, then about 3% HCl in MeOH to provide 4-bromo-N-(pyrimidin-4-yl)isoquinoline-7-sulfonamide (Intermediate OOOO) (0.125 g, 0.342 mmol, 24.29% yield) as a white solid (possibly HCl salt). m/z (ESI) 365.1 (M+H)+.

Workup

  1. additionTo a flask containing
  2. customproviding a white suspension
  3. stirringthe resulting mixture stirred for 1 hr
  4. customthe solution dried under reduced pressure
  5. customThe crude material was purified with a 40 g HP Silicycle column (SiliCycle, Inc. Quebec City, Canada)
  6. washto elute
  7. customMeOH in DCM (0 to 20%) providing product which
  8. customThe mixture was purified with a 10 g PE-AX column (Biotage AB, Uppsala, Sweden)
  9. washwashing with MeOH

Sources & evidence

ORD record
ord-b629214607a64eaba10e3762cbc073d4
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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