Aminopyrazine → HCID 57504331, compound

HRID 1097995Notes

Reaction equation

HRID 1097995 reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(OC(N(C)C)=[N+](C)C)[C:12]2[N:13]=[CH:14][CH:15]=C[C:11]=2[N:10]=N1.[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[N:32]1[C:36]2=[N:37][CH:38]=[N:39][C:40]([O:41][C@@H:42]([CH2:46][O:47][CH:48]([CH3:50])[CH3:49])[C:43](O)=[O:44])=[C:35]2[CH:34]=[N:33]1.NC1C=NC=CN=1.C(N(C(C)C)C(C)C)C>C(Cl)Cl.O>[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[N:32]1[C:36]2[N:37]=[CH:38][N:39]=[C:40]([O:41][CH:42]([CH2:46][O:47][CH:48]([CH3:49])[CH3:50])[C:43]([NH:8][C:12]3[CH:11]=[N:10][CH:15]=[CH:14][N:13]=3)=[O:44])[C:35]=2[CH:34]=[N:33]1

Participants

7

Reactant 4

HCID 78747AminopyrazineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57504479HCID 57504479, compound2×

Product 1

HCID 57504331HCID 57504331, compoundYield 39.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (333 mg, 0.88 mmol) was added to (2S)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-isopropoxypropanoic acid (Intermediate D2) (300 mg, 0.80 mmol), aminopyrazine (CAS no. 5049-61-6) (84 mg, 0.88 mmol) and N-ethyldiisopropylamine (0.153 mL, 0.88 mmol) in DCM (15 mL) at room temperature under nitrogen. The resulting solution was stirred at room temperature for 24 hours. The reaction mixture was diluted with DCM (10 mL) and water (10 mL) and the organic phase separated using a phase separation cartridge and evaporated. The residue was purified using reverse phase chromatography, eluting with 25-75% acetonitrile in water to give 2-[1-(2-chlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-isopropoxy-N-pyrazin-2-yl-propanamide (142 mg, 39%). 1H NMR (400 MHz, CDCl3) 1.18-1.22 (6H, m), 3.70-3.78 (1H, m), 4.10 (2H, d), 6.08 (1H, t), 7.40-7.50 (2H, m), 7.51-7.55 (1H, m), 7.62-7.64 (1H, m), 8.24 (1H, s), 8.35 (1H, s), 8.60 (1H, s), 8.80 (1H, s), 9.58 (1H, s); (M+H)+=454; HPLC tR=2.26.

Workup

  1. customat room temperature
  2. customthe organic phase separated
  3. customa phase separation cartridge
  4. customevaporated
  5. customThe residue was purified
  6. washeluting with 25-75% acetonitrile in water

Sources & evidence

ORD record
ord-9c96d896ffac44138f7ca8191ea87572
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

Loading…