Aniline → HCID 136500839, compound

HRID 1055852Notes

Reaction equation

HRID 1055852 reaction equation
Cl.Cl[C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[C:6]([C:13]3[NH:22][C:16]4[N:17]=[CH:18][NH:19][C:20](=[O:21])[C:15]=4[CH:14]=3)[CH:7]=[CH:8][CH:9]=2)[N:4]=1.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>>[C:24]1([NH:23][C:3]2[CH:12]=[CH:11][C:10]3[C:5](=[C:6]([C:13]4[NH:22][C:16]5[N:17]=[CH:18][NH:19][C:20](=[O:21])[C:15]=5[CH:14]=4)[CH:7]=[CH:8][CH:9]=3)[N:4]=2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

4

Reactant 3

HCID 6115AnilineHCID 2733832Lithium HexamethyldisilazideHCID 136500838HCID 136500838, compound

Product 1

HCID 136500839HCID 136500839, compoundYield 15.1%

Procedure

To 6-(2-chloroquinolin-8-yl)-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one hydrochloride (Example 19b; 0.075 g, 0.225 mmol) and aniline (0.144 ml, 1.576 mmol) was added LHMDS (1.0 M in THF; 1.576 ml, 1.576 mmol). After 1 h the reaction was partitioned between saturated aq. NH4Cl and EtOAc. The aq. layer was washed with saturated aq. NH4Cl and 1× brine, dried over Na2SO4, and concentrated in vacuo. The solid residue from the separatory funnel was rinsed with 10% DCM/MeOH into an Erlenmeyer flask, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulting solid was suspended in MeOH and filtered. The solid was collected to give 6-(2-(phenylamino)quinolin-8-yl)-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one (0.012 g, 0.034 mmol, 15% yield) as a dull-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.43 (1H, br. s), 11.80 (1H, br. s.), 9.59 (1H, s), 8.13 (1H, d, J=9.0 Hz), 8.02 (1H, dd, J=7.4, 1.6 Hz), 7.88 (1H, s), 7.78 (2H, dd, J=8.6, 1.2 Hz), 7.67-7.73 (1H, m), 7.28-7.38 (3H, m), 7.09-7.19 (2H, m), 6.97-7.05 (1H, m). m/z (ESI, +ve) 353.9 (M+H)+.

Workup

  1. customAfter 1 h the reaction was partitioned between saturated aq. NH4Cl and EtOAc
  2. washThe aq. layer was washed with saturated aq. NH4Cl and 1× brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. washThe solid residue from the separatory funnel was rinsed with 10% DCM/MeOH into an Erlenmeyer flask
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. filtrationfiltered
  10. customThe solid was collected

Sources & evidence

ORD record
ord-8a143306b1a1441b965a6157985b29c0
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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