Triphenylphosphine → (3R,4R)-1-((4-(1-(3-fluorobenzyl)-1H-indazole-5-ylamino)quinazolin-5-yl)methyl)-4-aminopiperidin-3-ol

HRID 900324Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:37]=[CH:38][CH:39]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][C:24]=4[CH2:26][N:27]4[CH2:32][CH2:31][C@@H:30]([N:33]=[N+]=[N-])[C@H:29]([OH:36])[CH2:28]4)[N:19]=[CH:18][N:17]=3)=[CH:12][CH:13]=2)[CH:8]=[N:7]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]([CH:37]=[CH:38][CH:39]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([NH:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][C:24]=4[CH2:26][N:27]4[CH2:32][CH2:31][C@@H:30]([NH2:33])[C@H:29]([OH:36])[CH2:28]4)[N:19]=[CH:18][N:17]=3)=[CH:12][CH:13]=2)[CH:8]=[N:7]1

Participants

Conditions

Temperature: 70 °C

Procedure

19A (78.0 mg, 0.15 mmol) was dissolved in a mixture of THF/H2O (1.2 ml/0.2 ml) and PPh3 (60.0 mg, 0.23 mmol) was added. The mixture was heated at 70° C. for 2 h. After cooled to rt, the reaction mixture was concentrated in vacuo and purified by prep HPLC to give 19B (85.0 mg, 93%) as a TFA salt. It has an analytical HPLC retention time=1.84 min (Chromolith SpeedROD column 4.6×50 mm, 10-90% aqueous methanol containing 0.1% TFA over 4 minutes, 4 mL/min, monitoring at 254 nm) and a LC/MS M++H=498+.

Workup

additionwas added
temperatureAfter cooled to rt
concentrationthe reaction mixture was concentrated in vacuo
custompurified by prep HPLC

Sources & evidence

ORD record: ord-a3b1dff0759d4df088c6e951e956b090
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07358256B2

Reaction notes

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