Diisopropylethylamine → tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-{5-[({6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-2,3-dihydrofuro[2,3-b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate

HRID 1499593ノート

反応式

HRID 1499593 の反応式
[NH2:1][C:2]1[C:3]([N:11]2[CH2:16][C@H:15]([CH3:17])[C@@H:14]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[C@H:13]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:12]2)=[C:4]2[CH2:10][CH2:9][O:8][C:5]2=[N:6][CH:7]=1.[F:34][C:35]1[CH:40]=[C:39]([C:41]([OH:44])([CH3:43])[CH3:42])[CH:38]=[C:37]([F:45])[C:36]=1[C:46]1[N:51]=[C:50]([C:52](O)=[O:53])[CH:49]=[CH:48][C:47]=1[F:55].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Si:19]([O:18][C@@H:14]1[C@@H:15]([CH3:17])[CH2:16][N:11]([C:3]2[C:2]([NH:1][C:52]([C:50]3[CH:49]=[CH:48][C:47]([F:55])=[C:46]([C:36]4[C:35]([F:34])=[CH:40][C:39]([C:41]([OH:44])([CH3:43])[CH3:42])=[CH:38][C:37]=4[F:45])[N:51]=3)=[O:53])=[CH:7][N:6]=[C:5]3[O:8][CH2:9][CH2:10][C:4]=23)[CH2:12][C@H:13]1[NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])([C:22]([CH3:23])([CH3:25])[CH3:24])([CH3:20])[CH3:21]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666524436-(2,6-Difluoro-4-(2-hydroxypropan-2-yl)phenyl)-5-fluoropicolinic acidHCID 86726732tert-Butyl ((3R,4R,5S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate

生成物 1

HCID 86726808tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-{5-[({6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-2,3-dihydrofuro[2,3-b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of tert-butyl ((3R,4R,5S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate (200 mg, 0.418 mmol), 6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridine-2-carboxylic acid (130 mg, 0.418 mmol), HATU (318 mg, 0.836 mmol) in DMF (1.5 mL) and DIPEA (218 μL, 1.25 mmol) was stirred at room temperature for 2 h. After quenched with water, the mixture was extracted with EtOAc (2×). The combined organic phases were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by purified by column chromatography on silica gel using CombiFlash® apparatus eluting with EtOAc/hexanes (50-100%), to yield an amide intermediate, tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-1-{5-[({6-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-2,3-dihydrofuro[2,3-b]pyridin-4-yl}-5-methylpiperidin-3-yl)carbamate.

後処理

  1. customAfter quenched with water
  2. extractionthe mixture was extracted with EtOAc (2×)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified
  7. customby purified by column chromatography on silica gel using CombiFlash® apparatus
  8. washeluting with EtOAc/hexanes (50-100%)

出典と根拠

ORDレコード
ord-f17af5091c2645c6aff93345bbb40e45
出典データセット
uspto-grants-2015_12
特許番号
US09200004B2

反応ノート

読み込み中…