Trifluoroacetic acid → HCID 58709804, compound

HRID 2375876Notes

Reaction equation

HRID 2375876 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:24][C:25]1[CH:26]=[C:27]([NH2:38])[CH:28]=[C:29]([N:31]2[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]2)[CH:30]=1.FC(F)(F)C(O)=O.C(N(CC)C(C)C)(C)C.[C:55]([N:59]=C=O)([CH3:58])([CH3:57])[CH3:56]>CN(C=O)C>[C:55]([NH:59][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:38][C:27]4[CH:28]=[C:29]([N:31]5[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]5)[CH:30]=[C:25]([Cl:24])[CH:26]=4)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:58])([CH3:57])[CH3:56]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 62412tert-Butyl isocyanateHCID 81531DiisopropylethylamineHCID 58709797tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydropyridine-1(2H)-carboxylateHCID 58709802HCID 58709802, compound

Product 1

HCID 58709804HCID 58709804, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °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 (88.0 mg, 0.263 mmol), 3-chloro-5-(4-methylpiperazin-1-yl)-phenylamine (71.2 mg, 0.316 mmol), trifluoroacetic acid (243 μL, 3.16 mmol), and DMF (2 mL) was stirred in a sealed tube at 80° C. for 16 h. After cooling, N,N-diisopropylethylamine (550 μL, 3.16 mmol) was added, and the mixture turned into a dark clear solution. Into above solution was added tert-butyl isocyanate (36.0 μL, 0.316 mmol) and the solution was stirring at rt for 1 h. After that time, the mixture was concentrated in vacuo to obtain dark-brown oil that was submitted for MS-directed purification to obtain a light-brown oil. Further purification by HPLC gave the title compound as an off-white powder. 1H NMR (DMSO-d6, 400 MHz): δ=1.29 (s, 9H), 2.23 (s, 3H), 2.46 (t, 4H, J=4.6 Hz), 3.18 (t, 4H, J=4.8 Hz), 3.53 (t, 2H, J=5.4 Hz), 4.00 (brs, 2H), 5.79 (s, 1H), 6.43 (s, 1H), 6.63 (d, 1H, J=1.6 Hz), 6.78 (s 1H), 7.30 (s, 1H), 7.75 (d, 1H, J=1.6 Hz), 8.32 (s, 1H), 9.27 (s, 1H), 11.98 (s, 1H). MS (ES+): m/z 522.98/525.01(100/33) [MH+]. HPLC: tR=2.13 min (ZQ2000, polar—5 min).

Workup

  1. temperatureAfter cooling
  2. stirringthe solution was stirring at rt for 1 h
  3. concentrationAfter that time, the mixture was concentrated in vacuo
  4. customto obtain dark-brown oil that
  5. customwas submitted for MS-directed purification
  6. customto obtain a light-brown oil
  7. customFurther purification by HPLC

Sources & evidence

ORD record
ord-270376ee60e14afaa6e64e3b3725f471
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

Loading…