Hydrochloric Acid → HCID 58709974, compound

HRID 2375909Notes

Reaction equation

HRID 2375909 reaction equation
[CH3:1][N:2]([CH3:17])[CH2:3][CH2:4][N:5]1[C:9]([C:10]2[CH:11]=[C:12]([NH2:16])[CH:13]=[CH:14][CH:15]=2)=[CH:8][N:7]=[CH:6]1.Cl[C:19]1[N:20]=[CH:21][C:22]2[CH:27]=[C:26]([C:28]3[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:32][CH:33]=3)[NH:25][C:23]=2[N:24]=1.Cl.C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.C(N(CC)C(C)C)(C)C>C(O)CCC.CCOCC.CN(C=O)C>[CH3:1][N:2]([CH3:17])[CH2:3][CH2:4][N:5]1[C:9]([C:10]2[CH:11]=[C:12]([NH:16][C:21]3[C:22]4[CH:27]=[C:26]([C:28]5[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:32][CH:33]=5)[NH:25][C:23]=4[N:24]=[CH:19][N:20]=3)[CH:13]=[CH:14][CH:15]=2)=[CH:8][N:7]=[CH:6]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 58710088HCID 58710088, compoundHCID 86607818HCID 86607818, compound

Product 1

HCID 58709974HCID 58709974, compound

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

3-[3-(2-Dimethylaminoethyl)-3H-imidazol-4-yl]phenylamine (110 mg, 0.478 mmol) was added to a solution of tert-butyl 4-(chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (133 mg, 0.398 mmol) in 1-butanol (2.0 mL). The reaction was stirred at 120° C. for 48 h. 0.8 mL of 1 N HCl in ether was then added and the mixture was stirred further at 120° C. for 15 h. LC-MS showed the displacement reaction was complete and the BOC group in the desired product was completely removed. Di-tert-butyldicarbonate (347 mg, 1.59 mmol) and N,N-diisopropylethylamine (0.347 mL, 1.99 mmol) were added, and the resulting mixture was stirred at rt for 30 min. DMF (z1.5 mL) was added and the mixture was filtered. The filtrate was purified by HPLC purification to give the title compound. 1H-NMR (CD3OD, 400 MHz): δ=1.50 (s, 9H), 2.52 (s, 6H), 2.58 (m, 2H), 3.04 (t, J=6.8 Hz, 2H), 3.67 (m, 2H), 4.13 (m, 2H), 4.53 (t, J=6.8 Hz, 2H), 6.30 (s, br, 1H), 6.72 (s, 1H), 7.18 (s, 1H), 7.19 (d, J=7.6 Hz, 1H), 7.48-7.52 (m, 1H), 7.72 (dd, J=2.4, 8.0 Hz, 1H), 8.06 (s, 1H), 8.12 (m, 1H), 8.26 (s, 1H). MS (ES+): m/z 529 [MH+]. HPLC: tR=2.00 min (ZQ2000, polar—5 min).

Workup

  1. stirringthe mixture was stirred further at 120° C. for 15 h
  2. customthe displacement reaction
  3. customthe BOC group in the desired product was completely removed
  4. stirringthe resulting mixture was stirred at rt for 30 min
  5. filtrationthe mixture was filtered
  6. customThe filtrate was purified by HPLC purification

Sources & evidence

ORD record
ord-6e20224b738c46b09f52c5df61d32c5f
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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