Chlorosulfamic acid → HCID 58346566, compound

HRID 222054Notes

Reaction equation

HRID 222054 reaction equation
CC(N(C)C)=O.[Cl:7][C:8]1[CH:9]=[C:10]([NH:23][C:24]2[C:29]3[C:30]4[CH2:38][CH2:37][C:36]5[C:32](=[CH:33][N:34]([CH2:39][CH2:40][OH:41])[N:35]=5)[C:31]=4[S:42][C:28]=3[N:27]=[CH:26][N:25]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=1.Cl[S:44]([NH2:47])(=[O:46])=[O:45]>[Cl-].[Na+].O>[S:44](=[O:46])(=[O:45])([O:41][CH2:40][CH2:39][N:34]1[CH:33]=[C:32]2[C:36]([CH2:37][CH2:38][C:30]3[C:29]4[C:24]([NH:23][C:10]5[CH:11]=[CH:12][C:13]([O:14][CH2:15][C:16]6[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=6)=[C:8]([Cl:7])[CH:9]=5)=[N:25][CH:26]=[N:27][C:28]=4[S:42][C:31]=32)=[N:35]1)[NH2:47]

Participants

5

Reactant 3

HCID 24499Chlorosulfamic acidHCID 31374DimethylacetamideHCID 58346526HCID 58346526, compound

Product 1

HCID 58346566HCID 58346566, compoundYield 26.3%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

To 5 mL DMA cooled to 5° C. was added 2-[6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-4,5-dihydro-2H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-2-yl]ethanol (100 mg, 0.19 mmol) followed by chlorosulfonyl amine (221 mg, 1.9 mmol). The mixture was stirred with warming to rt over a 2 h period, after which time stirring was halted. The entire mixture was poured onto cold brine (10 mL), upon which precipitation of a solid occurs. The mixture was filtered, and the filtrate extracted with CH2Cl2 (3×10 mL). The combined organic layers were dried over MgSO4, filtered, and the solvent removed under reduced pressure. The crude residue was purified by reverse phase HPLC. The product fractions were combined and diluted with CH2Cl2 (50 mL), and neutralized with NaHCO3 (50 mL). The organic layer was dried over MgSO4, filtered, and the solvent removed under reduced pressure to afford the final pure product (30 mg, 26%) as a white solid. 1H-NMR (DMSO-d6) δ 8.40 (s, 1H), 8.33 (s, 1H), 7.98 (s, 1H), 7.75 (s, 1H), 7.59 (s, 2H), 7.51 (dd, 1H), 7.40 (dd, 1H), 6.91-7.11 (m, 4H), 5.21 (s, 2H), 4.38 (br s, 4H), 3.32 (t, 2H), 2.90 (t, 2H); LCMS RT=3.45 min; [M+H]+=601.2.

Workup

  1. stirringafter which time stirring
  2. filtrationThe mixture was filtered
  3. extractionthe filtrate extracted with CH2Cl2 (3×10 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe crude residue was purified by reverse phase HPLC
  8. additiondiluted with CH2Cl2 (50 mL)
  9. dry with materialThe organic layer was dried over MgSO4
  10. filtrationfiltered
  11. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-bb6613a3b54e465aa6e81add58f3d5ed
Source dataset
uspto-grants-2012_06
Patent number
US08207172B2

Reaction notes

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