Triphenylphosphine → (1-Benzenesulfonyl-1H-indol-5-yl)-[6-(3-imidazol-1-yl-prop-1-ynyl)-quinazolin-4-yl]-amine

HRID 1264050Notes

Reaction equation

HRID 1264050 reaction equation
[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([NH:19][C:20]4[C:29]5[C:24](=[CH:25][CH:26]=[C:27](I)[CH:28]=5)[N:23]=[CH:22][N:21]=4)=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:31]([N:34]1[CH:38]=[CH:37][N:36]=[CH:35]1)[C:32]#[CH:33].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CCN(CC)CC.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([NH:19][C:20]4[C:29]5[C:24](=[CH:25][CH:26]=[C:27]([C:33]#[C:32][CH2:31][N:34]6[CH:38]=[CH:37][N:36]=[CH:35]6)[CH:28]=5)[N:23]=[CH:22][N:21]=4)=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 125919421-(prop-2-yn-1-yl)-1H-imidazoleHCID 15450144(1-Benzenesulfonyl-1H-indol-5-yl)-(6-iodo-quinazolin-4-yl)-amine

Product 1

HCID 18616501(1-Benzenesulfonyl-1H-indol-5-yl)-[6-(3-imidazol-1-yl-prop-1-ynyl)-quinazolin-4-yl]-amineYield 51%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

Quinazoline 14 (150 mg, 0.28 mmol), 1-N-2-propynylimidazole (200 mg, 1.89 mmol), Pd(OAc)2 (4 mg, 0.016 mmol) and PPh3 (9 mg, 0.033 mmol) were mixed in NEt3 (1.25 mL) and DMF (0.5 mL). The mixture was heated at 80° C under N2 for 16 hours. Upon cooling the black suspension was concentrated under reduced pressure and the residue dissolved in MeOH. Silica gel (1 g) was added and the methanol removed in vacuo. The resulting silica gel was placed atop a silica gel (40g) column which was then eluted with 200 mL 50:1 CH2Cl2:MeOH, the 300 mL 25:1 CH2Cl2 to provide alkyne 15 (72 mg, 51%) as a yellow foam. 1H NMR (CDCl3; 400 MHz): δ: 8.95 (br, 1H, NH), 8.63 (s, 1H), 8.62 (s, 1H), 8.24 (s, 1H), 7.96 (d, 1H, J=1.7 Hz), 7.84 (m, 3H), 7.71 (m, 2H), 7.51 (m, 3H), 7.41 (m, 2H), 7.14 (s, 1H), 7.10 (s, 1H), 6.55 (d, 1H, J=3.5 Hz), 5.01 (s, 2H).

Workup

  1. temperatureUpon cooling the black suspension
  2. concentrationwas concentrated under reduced pressure
  3. dissolutionthe residue dissolved in MeOH
  4. additionSilica gel (1 g) was added
  5. customthe methanol removed in vacuo
  6. washwas then eluted with 200 mL 50:1 CH2Cl2

Sources & evidence

ORD record
ord-55ae7b210f0648e7913e32b905c97d43
Source dataset
uspto-grants-2003_04
Patent number
US06541481B2

Reaction notes

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