Ammonium Chloride → HCID 46175430, compound

HRID 1098023Notes

Reaction equation

HRID 1098023 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH:27]1[CH2:30][N:29]([CH2:31][C@H:32]([O:43][C:44]2[N:49]=[CH:48][N:47]=[C:46]3[N:50]([C:53]4[C:58]([Cl:59])=[CH:57][CH:56]=[CH:55][N:54]=4)[N:51]=[CH:52][C:45]=23)[C:33]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][N:37]=2)=[O:34])[CH2:28]1)(C(C)(C)C)(C)C.[Cl-].[NH4+]>C1COCC1.C(Cl)Cl>[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([NH:35][C:33](=[O:34])[C@@H:32]([O:43][C:44]2[C:45]3[CH:52]=[N:51][N:50]([C:53]4[C:58]([Cl:59])=[CH:57][CH:56]=[CH:55][N:54]=4)[C:46]=3[N:47]=[CH:48][N:49]=2)[CH2:31][N:29]2[CH2:28][CH:27]([OH:26])[CH2:30]2)=[N:37][CH:38]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 57504519HCID 57504519, compound

Product 1

HCID 46175430HCID 46175430, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1M in THF) (5.96 mL, 5.96 mmol) was added to (2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (Intermediate AD1) (3.67 g, 5.96 mmol) in THF (75 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 20 hours, saturated ammonium chloride (50 mL) added, diluted with DCM (100 mL) and poured onto a phase separator. The organic layer was evaporated and the crude product was purified by flash silica chromatography, eluting with 0 to 10% MeOH in EtOAc to afford the product (1.7 g, 57%). 1H NMR (400 MHz, DMSO) δ 2.95-3.10 (3H, m), 3.10-3.15 (1H, m), 3.60-3.70 (2H, m), 4.14-4.21 (1H, m), 5.26 (1H, d), 5.73-5.75 (1H, m), 7.74 (1H, dd), 7.88 (1H, dd), 8.01-8.07 (1H, m), 8.33 (1H, dd), 8.39-8.40 (1H, m), 8.55 (1H, s), 8.66 (1H, s), 8.68 (1H, dd), 11.13 (1H, s); m/z (ESI+) (M+H)+=501; HPLC tR=1.27 min.

Workup

  1. additionpoured onto a phase separator
  2. customThe organic layer was evaporated
  3. customthe crude product was purified by flash silica chromatography
  4. washeluting with 0 to 10% MeOH in EtOAc

Sources & evidence

ORD record
ord-349de026855047b0939bb50ac36e84e4
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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