Hydrochloric Acid → HCID 178459711, compound

HRID 1958397Notes

Reaction equation

HRID 1958397 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([S:14][C:15]2[N:20]=[CH:19][N:18]=[C:17]3[N:21](C4C=CC(S(C)(=O)=O)=CC=4F)[N:22]=[CH:23][C:16]=23)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])C.Cl.Cl.[F:37][C:38]1[CH:43]=[C:42]([S:44]([CH3:47])(=[O:46])=[O:45])[CH:41]=[CH:40][C:39]=1N1C2=NC=NC(SC3CCNCC3)=C2C=N1.C(N(CC)CC)C.ClC(OC(C)C)=O>CN(C=O)C.C1(C)C=CC=CC=1>[CH:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([SH:14]([C:39]2[CH:40]=[CH:41][C:42]([S:44]([CH3:47])(=[O:46])=[O:45])=[CH:43][C:38]=2[F:37])[C:15]2[N:20]=[CH:19][N:18]=[C:17]3[NH:21][N:22]=[CH:23][C:16]=23)[CH2:10][CH2:9]1)=[O:7])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 21897830HCID 21897830, compoundHCID 536304101,1-Dimethylethyl 4-[[1-[2-fluoro-4-(methylsulfonyl)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-yl]thio]-1-piperidinecarboxylate

Product 1

HCID 178459711HCID 178459711, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

4-[1-(2-Fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylsulfanyl]-piperidine-1-carboxylic acid tert-butyl ester (3.54 g, 6.97 mmol) was treated with 4M HCl in 1,4-dioxanes (40 mL). After 2 hours stirring at room temperature, 1-(2-fluoro-4-methanesulfonyl-phenyl)-4-(piperidin-4-ylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride was collected by filtration. To a mixture of 1-(2-fluoro-4-methanesulfonyl-phenyl)-4-(piperidin-4-ylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride (3.0 g, 6.76 mmol) in DMF (27 mL) was added triethyl amine (2.05 g, 20.28 mmol). After 30 minutes stirring, isopropyl chloroformate (7.44 mmol) as a 1.0 M solution in toluene was added to the reaction and reaction was stirred for two hours. HCl salts had crashed out and were removed by filtration. Filtrate was extracted with ethyl acetate (100 mL) and washed with water (4×100 mL). Organic was dried over anhydrous MgSO4, filtered and concentrated in vacuo to yield Compound A214 as a white solid. 1H NMR (CDCl3, 400 MHz) δ 1.27 (d, J=6.3 Hz, 6H), 1.77 (2H, m), 2.18 (2H, m), 3.13 (3H, s), 3.21 (2H, m), 4.04 (2H, m), 4.48-4.40 (1H, m), 4.99-4.90 (1H, m), 7.98-7.92 (3H, m), 8.30 (1H, s), 8.79 (1H, s). Exact mass calculated for C21H24FN5O4S2 493.1, found 494.3 (MH+).

Workup

  1. filtration1-(2-fluoro-4-methanesulfonyl-phenyl)-4-(piperidin-4-ylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride was collected by filtration
  2. stirringAfter 30 minutes stirring
  3. stirringwas stirred for two hours
  4. customwere removed by filtration
  5. extractionFiltrate was extracted with ethyl acetate (100 mL)
  6. washwashed with water (4×100 mL)
  7. dry with materialOrganic was dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield Compound

Sources & evidence

ORD record
ord-e2d1230a3732416bbf8ea13af5b865ed
Source dataset
uspto-grants-2013_04
Patent number
US08410119B2

Reaction notes

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