Tetrahydrofuran → 1-(Chloromethyl)-3-({5-[2-(dimethylamino)ethoxy]-5-hydroxyindol-2-yl}carbonyl)-2,3dihydro-1H-pyrrolo[3,2-f]quinoline

HRID 1829604Notes

Reaction equation

HRID 1829604 reaction equation
C1C[O:4]CC1.C(O[C:14]1[CH:15]=[C:16]2[N:26]([C:27]([C:29]3[NH:30][C:31]4[C:36]([CH:37]=3)=[CH:35][C:34]([O:38][CH2:39][CH2:40][N:41]([CH3:43])[CH3:42])=[CH:33][CH:32]=4)=[O:28])[CH2:25][CH:24]([CH2:44][Cl:45])[C:17]2=[C:18]2[C:23]=1[N:22]=[CH:21][CH:20]=[CH:19]2)C1C=CC=CC=1>O.[Pd]>[Cl:45][CH2:44][CH:24]1[C:17]2=[C:18]3[C:23](=[CH:14][CH:15]=[C:16]2[N:26]([C:27]([C:29]2[N:30]=[C:31]4[C:36]([CH:37]=2)=[CH:35][C:34]([O:38][CH2:39][CH2:40][N:41]([CH3:42])[CH3:43])([OH:4])[CH:33]=[CH:32]4)=[O:28])[CH2:25]1)[N:22]=[CH:21][CH:20]=[CH:19]3

Participants

5

Reactant 2

HCID 8028TetrahydrofuranHCID 220534002-[(2-{[5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-pyrrolo[3,2-f]quinolin-3-yl]carbonyl}-1H-indol-5-yl)oxy]-N,N-dimethylethanamine

Product 1

HCID 220533851-(Chloromethyl)-3-({5-[2-(dimethylamino)ethoxy]-5-hydroxyindol-2-yl}carbonyl)-2,3dihydro-1H-pyrrolo[3,2-f]quinolineYield 93%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

THF (8 mL) then HCO2N4 (0.23 g, 3.6 mmol) in H2O (1 mL) were added to cooled (0° C.) mixture of 17b (0.20 g 036 mmol) and 10% Pd/C (0.1 g) under N2. The mixture was stirred at 0° C. for 14 h, and was then filtered through Celite. The Celite was washed with CH2Cl2/H2O. The aqueous layer was extracted with CH2Cl2(×3). The CH2Cl2 extracts were dried (brine, Na2SO4) and passed through a short plug of silica gel to give 18b (0.16 g, 93%) as a yellow solid: mp 209–215° C.; 1H NMR [(CD3)2SO]δ 11.66 (s, 1 H), 10.02 (bs, 1 H), 8.76 (dd, J=4.1, 1.4, 1 H), 8.41 (dd, J=8.5, 1.3, 1 H), 8.07 (s, 1 H), 7.56 (dd, J=8.5, 4.1, 1 H), 7.40 (d, J=8.9, 1 H), 7.17 (d, J=2.2, 1 H), 7.11 (d, J=1.2, 1 H,) 6.93 (dd, J=8.9, 2.3, 1 H), 4.82 (dd, J=10.7, 9.6, 1 H), 4.57 (dd, J=11.0, 2.1, 1 H), 4.29 (m, 1 H), 4.06 (t, J=5.9, 2 H), 4.04 (m, 1 H), 3.91 (dd, J=11.1, 7.2, 1 H), 2.64 (t, J=5.8, 2 H), 2.28 (s, 6 H); 13C NMR [(CD3)2SO]δ 160.3, 153.9, 153.0, 146.4, 142.8, 136.1, 131.6, 130.7, 127.4, 124.8, 124.7, 122.5, 116.0, 114.6, 113.1, 105.5, 103.1, 103.0, 66.1, 57.8, 54.9, 47.7, 45.5, 40.7.

Workup

  1. temperatureto cooled
  2. filtrationwas then filtered through Celite
  3. washThe Celite was washed with CH2Cl2/H2O
  4. extractionThe aqueous layer was extracted with CH2Cl2(×3)
  5. dry with materialThe CH2Cl2 extracts were dried (brine, Na2SO4)

Sources & evidence

ORD record
ord-0ecbcbd580fd46faa2120a3da2c488c8
Source dataset
uspto-grants-2006_06
Patent number
US07064117B2

Reaction notes

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