Diisopropylethylamine → 4-{(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}-3-[({6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

HRID 1499584ノート

反応式

HRID 1499584 の反応式
[C:1]([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH2:29])[C:13]([N:14]3[CH2:19][C@H:18]([CH3:20])[CH2:17][C@H:16]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=[O:3])[CH3:2].[F:30][C:31]1[CH:36]=[C:35]([CH2:37][O:38][CH3:39])[CH:34]=[C:33]([F:40])[C:32]=1[C:41]1[N:46]=[C:45]([C:47](O)=[O:48])[CH:44]=[CH:43][C:42]=1[F:50].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>[C:1]([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH:29][C:47]([C:45]3[CH:44]=[CH:43][C:42]([F:50])=[C:41]([C:32]4[C:31]([F:30])=[CH:36][C:35]([CH2:37][O:38][CH3:39])=[CH:34][C:33]=4[F:40])[N:46]=3)=[O:48])[C:13]([N:14]3[CH2:19][C@H:18]([CH3:20])[CH2:17][C@H:16]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=[O:3])[CH3:2]

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 706549716-(2,6-Difluoro-4-(methoxymethyl)phenyl)-5-fluoropicolinic acidHCID 867267483-Amino-4-{(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

生成物 1

HCID 867268054-{(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}-3-[({6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 3-amino-4-{(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate (256 mg, 0.633 mmol), 6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridine-2-carboxylic acid (188 mg, 0.633 mmol), HATU (481 mg, 1.26 mmol) in DMF (1 mL) and DIPEA (0.330 mL, 1.90 mmol) was stirred at room temperature for 2 h. The reaction mixture was quenched with water and then extracted with EtOAc (2 times). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel using CombiFlash® apparatus eluting with EtOAc/hexanes (50-100%) to yield 4-{(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}-3-[({6-[2,6-difluoro-4-(methoxymethyl)phenyl]-5-fluoropyridin-2-yl}carbonyl)amino]-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate as an intermediate.

後処理

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with EtOAc (2 times)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by column chromatography on silica gel using CombiFlash® apparatus
  7. washeluting with EtOAc/hexanes (50-100%)

出典と根拠

ORDレコード
ord-0146c2c8c8d74c7ea9bc0b5f6140d94b
出典データセット
uspto-grants-2015_12
特許番号
US09200004B2

反応ノート

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