Methylamine → 5-(benzyloxy)-2-(4-fluorophenyl)-N-methylfuro[2,3-c]pyridine-3-carboxamide

HRID 44066ノート

反応式

HRID 44066 の反応式
CN.C[CH2:4][N:5](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:36]([O:43][C:44]1[CH:45]=[C:46]2[C:52]([C:53]([OH:55])=O)=[C:51]([C:56]3[CH:61]=[CH:60][C:59]([F:62])=[CH:58][CH:57]=3)[O:50][C:47]2=[CH:48][N:49]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CN(C=O)C>[CH2:36]([O:43][C:44]1[CH:45]=[C:46]2[C:52]([C:53]([NH:5][CH3:4])=[O:55])=[C:51]([C:56]3[CH:57]=[CH:58][C:59]([F:62])=[CH:60][CH:61]=3)[O:50][C:47]2=[CH:48][N:49]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

参加物

6

反応物 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674077135-(Benzyloxy)-2-(4-fluorophenyl)furo[2,3-c]pyridine-3-carboxylic acid

生成物 1

HCID 672175935-(benzyloxy)-2-(4-fluorophenyl)-N-methylfuro[2,3-c]pyridine-3-carboxamide収率 39%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Methanamine (3.1 mL, 6.2 mmol, 2M in THF) was added to a stirring solution of DIEA (646 μL, 3.70 mmol), HATU (563 mg, 1.48 mmol), 5-(benzyloxy)-2-(4-fluorophenyl)furo[2,3-c]pyridine-3-carboxylic acid (448 mg, 1.23 mmol) in DMF (12 mL) at room temperature. The mixture concentrated then diluted with EtOAc and washed with sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) to give 5-(benzyloxy)-2-(4-fluorophenyl)-N-methylfuro[2,3-c]pyridine-3-carboxamide (180 mg, 39% yield) consistent by LCMS and NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.62 (1H, s), 8.37-8.45 (1 H, m), 7.98-8.08 (2H, m), 7.29-7.50 (7H, m), 7.06 (1H, s), 5.42 (2H, s), 2.83 (3 H, d, J=4.52 Hz). LC-MS retention time: 2.00 min; m/z (MH+): 377. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

後処理

  1. concentrationThe mixture concentrated
  2. additionthen diluted with EtOAc
  3. washwashed
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm)

出典と根拠

ORDレコード
ord-1d083c259b97469383468e0eb2bbe294
出典データセット
uspto-grants-2013_09
特許番号
US08536338B2

反応ノート

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