Phosphorus oxide (P4O10) → 6-(5,5-Dimethyl-4,5-dihydrooxazol-2-yl)-N-(4-fluorobenzyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide

HRID 40094Notes

Reaction equation

[F:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:18]3[C:13](=[CH:14][C:15]([C:19]([NH:21][CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])=O)=[CH:16][CH:17]=3)[N:12]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[C:11]=2[CH:34]([CH3:36])[CH3:35])=[O:9])=[CH:4][CH:3]=1.C(N1C2C(=CC=C(C(NCC(O)(C)C)=O)C=2)C(C(NCC2C=CC(F)=C(F)C=2)=O)=C1C(C)C)C1C=CC=CC=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>C1C=CC=CC=1>[CH3:25][C:23]1([CH3:24])[O:26][C:19]([C:15]2[CH:14]=[C:13]3[C:18]([C:10]([C:8]([NH:7][CH2:6][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:38][CH:37]=4)=[O:9])=[C:11]([CH:34]([CH3:36])[CH3:35])[N:12]3[CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[CH:17][CH:16]=2)=[N:21][CH2:22]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of N3-(4-fluorobenzyl)-N6-(2-hydroxy-2-methylpropyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indole-3,6-dicarboxamide (Compound 68, 23 mg, 0.043 mmol) in benzene (6 ml) at 25° C. was added P2O5 (120 mg, 0.86 mmol). The mixture was stirred at 50° C. for 4 h, quenched with 6N NaOH (1 ml), extracted several times with EtOAc, washed with H2O, brine, dried over Na2SO4, concentrated in vacuo. The residue was purified by chromatography on silica gel (100% EtOAc) to yield the title compound as yellow oil.

Workup

customquenched with 6N NaOH (1 ml)
extractionextracted several times with EtOAc
washwashed with H2O, brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by chromatography on silica gel (100% EtOAc)

Sources & evidence

ORD record: ord-f16ce2aadef3440c99be1112c3cf515b
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524917B2

Reaction notes

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