Tetrahydrofuran → 7-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-5-(3-ethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-2-one

HRID 2218268Notes

Reaction equation

HRID 2218268 reaction equation
[NH2:1][C:2]1[C:7]([CH2:8][OH:9])=[C:6]([C:10]2[CH:11]=[CH:12][C:13]([NH:17][CH2:18][CH3:19])=[C:14]([OH:16])[CH:15]=2)[CH:5]=[C:4]([C:20]2[C:25]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)=[CH:24][CH:23]=[CH:22][C:21]=2[O:36][CH2:37][CH:38]2[CH2:40][CH2:39]2)[N:3]=1.C(N(CC)CC)C.Cl[C:49](Cl)([O:51]C(=O)OC(Cl)(Cl)Cl)Cl.C1C[O:63][CH2:62]C1>>[CH:38]1([CH2:37][O:36][C:21]2[CH:22]=[CH:23][CH:24]=[C:25]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)[C:20]=2[C:4]2[CH:5]=[C:6]([C:10]3[CH:11]=[CH:12][C:13]4[N:17]([CH2:18][CH3:19])[C:62](=[O:63])[O:16][C:14]=4[CH:15]=3)[C:7]3[CH2:8][O:9][C:49](=[O:51])[NH:1][C:2]=3[N:3]=2)[CH2:39][CH2:40]1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 94429TriphosgeneHCID 691449515-[2-Amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-3-(hydroxymethyl)-4-pyridinyl]-2-(ethylamino)phenol

Product 1

HCID 691468257-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-5-(3-ethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-2-one

Procedure

To a cold (0° C.) solution of 5-[2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-3-(hydroxymethyl)-4-pyridinyl]-2-(ethylamino)phenol (0.150 g, 0.28 mmol) in THF (5.0 mL) including triethylamine (0.12 mL, 0.83 mmol) was added triphosgene (0.099 g, 0.33 mmol). After being stirred for 30 minutes, the mixture was allowed to warm to room temperature, and the stirring was continued overnight. The resulting mixture was quenched with water and extracted with ethyl acetate. The separated organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane:methanol, 9:1) to give 7-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-5-(3-ethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-6-yl)-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-2-one. (0.049 g, 30%); LC-MS (m/z=594, M+1)

Workup

  1. waitthe stirring was continued overnight
  2. customThe resulting mixture was quenched with water
  3. extractionextracted with ethyl acetate
  4. washThe separated organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel (dichloromethane:methanol, 9:1)

Sources & evidence

ORD record
ord-37e7bdcddcd44a2ea9dd2e6f44a544e4
Source dataset
uspto-grants-2008_08
Patent number
US07410986B2

Reaction notes

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