Tetrahydrofuran → HCID 16725627, compound

HRID 506388Notes

Reaction equation

HRID 506388 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22]([OH:40])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2].CC(C)([O-:46])C.[K+].[O:49]1[CH2:53][CH2:52][CH2:51]C1>>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:38])([F:39])[F:37])[CH:27]=3)[C:22]([O:40][CH2:51][CH2:52][C:53]([OH:49])=[O:46])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxideHCID 86610574(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-hydroxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

Product 1

HCID 16725627HCID 16725627, compound

Procedure

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-hydroxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (150 mg) is dissolved in tetrahydrofuran (3 ml), and thereto are added at room temperature potassium tert-butoxide (28 mg) and P-propiolactone (16 μl). The reaction solution is stirred overnight at room temperature, and then partitioned by adding ethyl acetate and 1N HCl. The organic layer is washed with saturated brine and dried over magnesium sulfate, then concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→9:1) and LC/MS (CAPCEL PAK MGII (SHISEIDO), water:methanol=60:40→0:100, 40 ml/min) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(2-carboxyethoxy)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (12 mg). MS (m/z): 672 [M+H]+.

Workup

  1. custompartitioned
  2. additionby adding ethyl acetate and 1N HCl
  3. washThe organic layer is washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by column chromatography (silica gel; chloroform:methanol=1:0→9:1) and LC/MS (CAPCEL PAK MGII (SHISEIDO), water:methanol=60:40→0:100, 40 ml/min)

Sources & evidence

ORD record
ord-91b2521bfdee4021beba0473c0cc1d6e
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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