Trifluoroacetic acid → HCID 58709949, compound

HRID 2375895Notes

Reaction equation

HRID 2375895 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:23][C:17]3[N:18]=[CH:19][N:20]=[C:21](Cl)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.Cl.[NH2:25][C:26]1[CH:27]=[CH:28][C:29](=[O:38])[N:30]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:31]=1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[C:53]([N:57]=C=O)([CH3:56])([CH3:55])[CH3:54]>CN(C)C=O.CS(C)=O>[C:53]([NH:57][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:23][C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH:25][C:26]4[CH:27]=[CH:28][C:29](=[O:38])[N:30]([C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=5)[CH:31]=4)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:56])([CH3:55])[CH3:54]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 62412tert-Butyl isocyanateHCID 58709797tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydropyridine-1(2H)-carboxylateHCID 69277665HCID 69277665, compound

Product 1

HCID 58709949HCID 58709949, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (54.5 mg, 0.163 mmol), 5-amino-1-phenyl-1H-pyridin-2-one hydrochloride (43.5 mg, 0.195 mmol), dimethyl sulfoxide (3 mL) and trifluoroacetic acid (125 μl, 1.63 mmol) in a sealed tube was heated at 100° C. overnight. The mixture was concentrated in vacuo and was charged with N,N-dimethylformamide (2 mL), triethylamine (272 μL, 1.95 mmol) and tert-butyl isocyanate (20.4 μl, 0.179 mmol). The above mixture was stirred at rt for 1.5 h, concentrated in vacuo, and partitioned between water/EtOAc (10 mL/15 mL). The aqueous phase was extracted with EtOAc (2×15 mL), and the combined organic phase was washed with brine (10 mL), concentrated in vacuo, and dissolved in DMSO/MeOH for submission for MS-directed purification, which gave the title compound as beige solid. 1H NMR (CD3OD, 400 MHz): δ=1.46 (s, 9H), 2.67 (brs, 2H), 3.69-3.72 (m, 2H), 4.16(brs, 2H), 6.41 (brs, 1H), 6.72 (s, 1H), 6.79 (d, 1H, J=9.6 Hz), 7.56-7.68 (m, 5H), 7.95 (dd, 1H, J=2.8 & 9.6 Hz), 8.27 (s, 1H), 8.39 (d, 1H, J=2.4 Hz), 8.64 (s, 1H). MS (ES+): m/z 484.09 (100) [MH+]. HPLC: tR=2.44 min (ZQ2000polar—5 min).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. concentrationconcentrated in vacuo
  3. custompartitioned between water/EtOAc (10 mL/15 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (2×15 mL)
  5. washthe combined organic phase was washed with brine (10 mL)
  6. concentrationconcentrated in vacuo
  7. dissolutiondissolved in DMSO/MeOH for submission for MS-directed purification, which

Sources & evidence

ORD record
ord-431bf7e5878d4c35acb9d04c97339f07
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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