Diisopropylethylamine → N-{4-[(3S)-3-Aminopiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide

HRID 1499428ノート

反応式

HRID 1499428 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][CH:11]=[C:12]([C:14]([OH:16])=O)[N:13]=1.[NH2:17][C:18]1[C:19]([N:27]2[CH2:32][CH2:31][CH2:30][C@H:29]([NH:33]C(=O)OC(C)(C)C)[CH2:28]2)=[C:20]2[CH2:26][CH2:25][O:24][C:21]2=[N:22][CH:23]=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>[NH2:33][C@H:29]1[CH2:30][CH2:31][CH2:32][N:27]([C:19]2[C:18]([NH:17][C:14]([C:12]3[N:13]=[C:9]([C:3]4[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])[S:10][CH:11]=3)=[O:16])=[CH:23][N:22]=[C:21]3[O:24][CH2:25][CH2:26][C:20]=23)[CH2:28]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 242784542-(2,6-Difluorophenyl)-1,3-thiazole-4-carboxylic acidHCID 86726677tert-Butyl [(3S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate

生成物 1

HCID 86726679N-{4-[(3S)-3-Aminopiperidin-1-yl]-2,3-dihydrofuro[2,3-b]pyridin-5-yl}-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide収率 20.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of 2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylic acid (Example 2, Step 2, 14.5 mg, 0.0601 mmol), tert-butyl [(3S)-1-(5-amino-2,3-dihydrofuro[2,3-b]pyridin-4-yl)piperidin-3-yl]carbamate (19.2 mg, 0.0574 mmol) and HATU (72.5 mg, 0.191 mmol), DMF (1.50 mL) was added, followed by DIPEA (79.6 mg, 0.616 mmol). The reaction mixture was stirred at room temperature for 2 h, and then concentrated under reduced pressure. To the 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 0.15% NH4OH, at flow rate of 30 mL/min.) to afford the title compound as a white solid (5.3 mg, 20%). LCMS calc. for C22H22F2N5O2S (M+H)+: m/z=458.1. found 458.1.

後処理

  1. additionwas added
  2. concentrationconcentrated under reduced pressure
  3. additionTo the 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 0.15% NH4OH, at flow rate of 30 mL/min.)

出典と根拠

ORDレコード
ord-ca798cd407b8442a810e45d220640fa5
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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