2-Amino-5-cyanopyridine → HCID 57504537, compound

HRID 1098215Notes

Reaction equation

HRID 1098215 reaction equation
C[Al](C)C.[NH2:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][N:7]=1.[Si:14]([O:21][CH2:22][C@H:23]([O:25][CH2:26][C@H:27]([O:32][C:33]1[N:38]=[CH:37][N:36]=[C:35]2[N:39]([C:42]3[C:47]([Cl:48])=[CH:46][CH:45]=[CH:44][N:43]=3)[N:40]=[CH:41][C:34]=12)[C:28](OC)=[O:29])[CH3:24])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+]>C(Cl)Cl.C1(C)C=CC=CC=1.CCOC(C)=O>[Si:14]([O:21][CH2:22][C@H:23]([O:25][CH2:26][C@H:27]([O:32][C:33]1[N:38]=[CH:37][N:36]=[C:35]2[N:39]([C:42]3[C:47]([Cl:48])=[CH:46][CH:45]=[CH:44][N:43]=3)[N:40]=[CH:41][C:34]=12)[C:28]([NH:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][N:7]=1)=[O:29])[CH3:24])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 8182602-Amino-5-cyanopyridineHCID 9855836Potassium sodium tartarateHCID 16682925TrimethylaluminumHCID 59279450HCID 59279450, compound

Product 1

HCID 57504537HCID 57504537, compoundYield 56.4%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Trimethylaluminium (2M in hexanes) (1.839 mL, 3.68 mmol) was added to 6-aminonicotinonitrile (CAS no. 4214-73-7) (411 mg, 3.45 mmol) in DCM (8 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (2S)-methyl 3-((R)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)propanoate (Intermediate AN2) (600 mg, 1.15 mmol) in toluene (8 mL) was added and the reaction was allowed to warm to room temperature and then heated to 100° C. for 5 hours in the microwave reactor. The reaction was allowed to cool to room temperature before adding EtOAc (50 mL) and 20% sodium potassium tartrate solution (30 mL), which was stirred vigorously for 16 hours. The phases were separated and the organic layer was washed with sat. brine (15 mL), dried (MgSO4) and evaporated. The crude product was purified by flash alumina chromatography, eluting with 0 to 50% EtOAc in isohexane to afford the product (395 mg, 56.4%). 1H NMR (400 MHz, DMSO) δ-0.01 (d, 6H), 0.80 (s, 9H), 1.08 (d, 3H), 3.47-3.62 (m, 2H), 3.67-3.77 (m, 1H), 4.09-4.21 (m, 2H), 5.92-5.97 (m, 1H), 7.75-7.80 (m, 1H), 8.13-8.17 (m, 1H), 8.22-8.29 (m, 1H), 8.34-8.37 (m, 1H), 8.58 (s, 1H), 8.63 (s, 1H), 8.67-8.71 (m, 1H), 8.82-8.85 (m, 1H), 11.55 (s, 1H); m/z (ES+), (M+H)+=607.47; HPLC tR=3.27 min

Workup

  1. temperatureto warm to room temperature
  2. temperatureheated to 100° C. for 5 hours in the microwave reactor
  3. temperatureto cool to room temperature
  4. stirringwas stirred vigorously for 16 hours
  5. customThe phases were separated
  6. washthe organic layer was washed with sat. brine (15 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe crude product was purified by flash alumina chromatography
  10. washeluting with 0 to 50% EtOAc in isohexane

Sources & evidence

ORD record
ord-7c60f4071fae41cebcce79e6212068b1
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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