Ammonium Chloride → (2S)-N-(5-cyanopyridin-2-yl)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-hydroxyethoxy)propanamide

HRID 1098051Notes

Reaction equation

HRID 1098051 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH2:37][CH2:38][O:39][CH2:40][C@H:41]([O:53][C:54]1[N:59]=[CH:58][N:57]=[C:56]2[N:60]([C:63]3[CH:68]=[CH:67][CH:66]=[C:65]([Cl:69])[C:64]=3[Cl:70])[N:61]=[CH:62][C:55]=12)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]#[N:52])=[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>[C:51]([C:48]1[CH:49]=[CH:50][C:45]([NH:44][C:42](=[O:43])[C@@H:41]([O:53][C:54]2[N:59]=[CH:58][N:57]=[C:56]3[N:60]([C:63]4[CH:68]=[CH:67][CH:66]=[C:65]([Cl:69])[C:64]=4[Cl:70])[N:61]=[CH:62][C:55]=23)[CH2:40][O:39][CH2:38][CH2:37][OH:36])=[N:46][CH:47]=1)#[N:52]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 57504551(2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-cyanopyridin-2-yl)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide

Product 1

HCID 57504431(2S)-N-(5-cyanopyridin-2-yl)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-(2-hydroxyethoxy)propanamideYield 80.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tetrabutylammonium fluoride (1M in THF) (0.701 mL, 0.70 mmol) was added dropwise to a stirred solution of (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-N-(5-cyanopyridin-2-yl)-2-(1-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanamide (440 mg, 0.58 mmol) in THF (15 mL) over a period of 1 minute. The resulting solution was 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 to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were concentrated to remove most of the MeCN and then EtOAc was added. The organic phase was washed sequentially with saturated NaHCO3 and water the organic layer was evaporated to dryness to afford the product (240 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 2.37 (1H, s), 3.81-3.62 (4H, m), 4.14 (2H, m), 6.00 (1H, t), 7.44-7.28 (2H, m), 7.60 (1H, dd), 7.90 (1H, dd), 8.29 (1H, dd), 8.36 (1H, s), 8.49 (1H, dd), 8.52 (1H, s), 9.26 (1H, s); m/z (ES+) (M+H)+=514; HPLC tR=2.13 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
  5. customto afford crude product
  6. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  7. additionFractions containing the desired compound
  8. concentrationwere concentrated
  9. customto remove most of the MeCN
  10. additionEtOAc was added
  11. washThe organic phase was washed sequentially with saturated NaHCO3 and water the organic layer
  12. customwas evaporated to dryness

Sources & evidence

ORD record
ord-2d9370ede8d14ee6b1e6e83ec1771eb1
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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