4-Methylmorpholine → phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl) heptanoyl]-1-pyrazolidinecarboxylate

HRID 1396942ノート

反応式

HRID 1396942 の反応式
[CH:1]([N:3]([CH2:12][C@@H:13]([CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[C:14]([N:16]1[C@H:20]([C:21]([OH:23])=O)[CH2:19][CH2:18][N:17]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])=[O:15])[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:2].CN1CCOCC1.F[B-](F)(F)F.COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[F:68][C:69]1[CH:70]=[CH:71][C:72]([NH2:75])=[N:73][CH:74]=1>C(#N)C>[F:68][C:69]1[CH:70]=[CH:71][C:72]([NH:75][C:21]([C@@H:20]2[CH2:19][CH2:18][N:17]([C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[O:25])[N:16]2[C:14](=[O:15])[C@@H:13]([CH2:12][N:3]([CH:1]=[O:2])[O:4][CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[O:23])=[N:73][CH:74]=1

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 27377012-Amino-5-fluoropyridineHCID 116312684-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborateHCID 86706375(3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

生成物 1

HCID 86706376phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl) heptanoyl]-1-pyrazolidinecarboxylate収率 69.4%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (1.015 g, 1.931 mmol) in acetonitrile (30 mL) at 0° C. was added 4-methylmorpholine (0.467 mL, 4.25 mmol), followed by 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium tetrafluoroborate (DMTMM) (0.559 g, 2.317 mmol). The solution was stirred for 15 min, then 5-fluoro-2-pyridinamine (0.260 g, 2.317 mmol) was added. The reaction mixture was warmed up to room temperature and stirred overnight. The solvent was evaporated, and the residue was dissolved in DCM. The solution was washed with 5% aq. NaHSO4 followed by water, and the organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford a crude oil which was purified by RP-HPLC to yield phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-pyrazolidinecarboxylate as a colorless gum (830 mg, 69%). LCMS: (M+H)+: 620.2.

後処理

  1. stirringstirred overnight
  2. customThe solvent was evaporated
  3. dissolutionthe residue was dissolved in DCM
  4. washThe solution was washed with 5% aq. NaHSO4
  5. dry with materialthe organic phase was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a crude oil which
  9. customwas purified by RP-HPLC

出典と根拠

ORDレコード
ord-612b4afefc244ba39b0c7ee8bdbe11e1
出典データセット
uspto-grants-2014_12
特許番号
US08901119B2

反応ノート

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