Ammonium Chloride → HCID 57504398, compound

HRID 1098024Notes

Reaction equation

HRID 1098024 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH2:37][CH2:38][O:39][CH2:40][C@H:41]([O:52][C:53]1[N:58]=[CH:57][N:56]=[C:55]2[N:59]([C:62]3[CH:67]=[CH:66][CH:65]=[C:64]([Cl:68])[C:63]=3[CH3:69])[N:60]=[CH:61][C:54]=12)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][N:46]=1)=[O:43])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[NH4+]>C1COCC1.CCOC(C)=O>[Cl:68][C:64]1[C:63]([CH3:69])=[C:62]([N:59]2[C:55]3[N:56]=[CH:57][N:58]=[C:53]([O:52][C@@H:41]([CH2:40][O:39][CH2:38][CH2:37][OH:36])[C:42]([NH:44][C:45]4[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][N:46]=4)=[O:43])[C:54]=3[CH:61]=[N:60]2)[CH:67]=[CH:66][CH:65]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 57504521HCID 57504521, compound

Product 1

HCID 57504398HCID 57504398, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tetrabutylammonium fluoride (1M in THF) (0.832 mL, 0.83 mmol) was added dropwise to a stirred solution of (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-chloro-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate AE3) (500 mg, 0.69 mmol) in THF (15 mL) over a period of 1 minute and the resulting solution stirred at ambient temperature for 3 hours. Saturated ammonium chloride (20 mL) was added to the reaction mixture which was then diluted with EtOAc (25 mL) and washed sequentially with water (25 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4), filtered and evaporated in vacuo. The crude product was purified by flash silica chromatography, elution gradient 60 to 100% EtOAc in isohexane. This was further purified by chiral HPLC to give the product (76 mg, 52%). 1H NMR (400 MHz, DMSO) δ 2.06 (3H, s), 2.24 (3H, s), 3.53-3.58 (2H, m), 3.58-3.68 (2H, m), 4.00-4.05 (1H, m), 4.08-4.13 (1H, m), 4.61 (1H, t), 5.93-6.01 (1H, m), 7.45-7.02 (2H, m), 7.57-7.60 (1H, m), 7.66-7.69 (1H, m), 7.88-7.95 (1H, m), 8.17-8.18 (1H, m), 8.54 (1H, s), 8.62 (1H, s), 10.86 (1H, s); m/z (ESI+) (M+H)+=483; HPLC tR=2.14 min.

Workup

  1. washwashed sequentially with water (25 mL) and saturated brine (25 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe crude product was purified by flash silica chromatography, elution gradient 60 to 100% EtOAc in isohexane
  6. customThis was further purified by chiral HPLC

Sources & evidence

ORD record
ord-67db2d04ab734b6bac8a0b8262c9da89
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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