Diisopropylethylamine → 3-Amino-N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide

HRID 1499498ノート

反応式

HRID 1499498 の反応式
C(OC([NH:8][C:9]1[C:10]([C:24]([OH:26])=O)=[N:11][C:12]([C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=2[F:23])=[C:13]([F:15])[CH:14]=1)=O)(C)(C)C.[NH2:27][C:28]1[C:29]([N:37]2[CH2:42][C@H:41]([CH3:43])[CH2:40][C@H:39]([NH:44]C(=O)OC(C)(C)C)[CH2:38]2)=[C:30]2[CH2:36][CH2:35][O:34][C:31]2=[N:32][CH:33]=1.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>[NH2:8][C:9]1[C:10]([C:24]([NH:27][C:28]2[C:29]([N:37]3[CH2:42][C@H:41]([CH3:43])[CH2:40][C@H:39]([NH2:44])[CH2:38]3)=[C:30]3[CH2:36][CH2:35][O:34][C:31]3=[N:32][CH:33]=2)=[O:26])=[N:11][C:12]([C:16]2[C:17]([F:23])=[CH:18][CH:19]=[CH:20][C:21]=2[F:22])=[C:13]([F:15])[CH:14]=1

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 86726720tert-Butyl [(3S,5R)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-5-methylpiperidin-3-yl]carbamateHCID 867267293-[(Tert-butoxycarbonyl)amino]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxylic acid

生成物 1

HCID 867267283-Amino-N-{4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide収率 29.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of 3-[(tert-butoxycarbonyl)amino]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxylic acid (16.1 mg, 0.0437 mmol), tert-butyl [(3S,5R)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-5-methylpiperidin-3-yl]carbamate (14.0 mg, 0.0402 mmol) and HATU (53.1 mg, 0.140 mmol), DMF (1.0 mL) was added followed by DIPEA (70.1 μL, 0.402 mmol). The reaction mixture was stirred at room temperature for 2 h, and then concentrated under reduced pressure. To the resulting residue, DCM (2.0 mL) was added, followed by TFA (2.0 mL). The mixture was stirred at room temperature for 30 min., and then concentrated under reduced pressure. The resulting residue was purified using RP-HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.) to afford the title compound as a white solid (5.9 mg, 29%). LCMS calc. for C25H26F3N6O2 (M+H)+: m/z=499.2. found 499.2.

後処理

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. additionTo the resulting residue, DCM (2.0 mL) was added
  4. stirringThe mixture was stirred at room temperature for 30 min.
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified
  7. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at flow rate of 30 mL/min.)

出典と根拠

ORDレコード
ord-f8594b1c8652410d97aef5a61f7acc30
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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