Hydrochloric Acid → HCID 66549231、化合物

HRID 2174383ノート

反応式

HRID 2174383 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:28]([F:31])([F:30])[F:29])[O:14][N:13]=[C:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH2:24][CH:23]([C:25]([OH:27])=O)[CH2:22]4)=[CH:17][CH:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].C1C=C[C:35]2N(O)N=[N:38][C:36]=2[CH:37]=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.Cl.C1(N)CC1>CN(C=O)C>[CH:36]1([NH:38][C:25]([CH:23]2[CH2:22][N:21]([C:18]3[CH:19]=[CH:20][C:15]([C:12]4[CH2:11][C:10]([C:4]5[CH:5]=[C:6]([Cl:9])[C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=5)([C:28]([F:30])([F:31])[F:29])[O:14][N:13]=4)=[CH:16][CH:17]=3)[CH2:24]2)=[O:27])[CH2:37][CH2:35]1

参加物

8

反応物 6

HCID 313Hydrochloric AcidHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86707796HCID 86707796、化合物

生成物 1

HCID 66549231HCID 66549231、化合物収率 33.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a stirred solution of 1-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-azetidine-3-carboxylic acid (Preparation 12, 0.1 g, 0.203 mmol) in DMF (3 mL) was added HOBt (0.027 g, 0.203 mmol), DIPEA (0.052 g, 0.406 mmol), EDCl.HCl (0.058 g, 0.304 mmol) and cyclopropyl amine (0.011 g, 0.203 mmol) at 0° C. Resulting reaction mixture was stirred at room temperature for 16 hours under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched with water (20 mL) and extracted with EtOAc (3×20 mL). Combined organic layer was washed with saturated NaHCO3 (2×50 mL), water (2×50 mL), brine (50 mL), dried over sodium sulphate and evaporated in vacuo to crude. Crude was purified by column chromatography on silica gel (100-200 mesh size). Compound was eluted using 1.1% methanol in DCM to afford white solid (0.036 g, 33%). 1H-NMR (400 MHz, CDCl3) δ: 0.49-0.53 (m, 2H), 0.77-0.87 (m, 2H), 2.74-2.77 (m, 1H), 3.31-3.34 (m, 1H), 3.61 (d, 1H, J=16.88 Hz), 4.01-4.07 (m, 5H), 5.72 (bs, 1H), 6.40 (d, 2H, J=8.68 Hz), 7.47 (d, 2H, J=8.68 Hz), 7.63 (s, 2H). LC-MS (m/z): [M−H] 529.70.

後処理

  1. customat 0° C
  2. customResulting
  3. customreaction mixture
  4. customAfter complete consumption of starting material, reaction mixture
  5. customwas quenched with water (20 mL)
  6. extractionextracted with EtOAc (3×20 mL)
  7. washCombined organic layer was washed with saturated NaHCO3 (2×50 mL), water (2×50 mL), brine (50 mL)
  8. dry with materialdried over sodium sulphate
  9. customevaporated in vacuo to crude
  10. customCrude was purified by column chromatography on silica gel (100-200 mesh size)
  11. washCompound was eluted

出典と根拠

ORDレコード
ord-b62e7eba01f2472c930191808b3f8075
出典データセット
uspto-grants-2015_06
特許番号
US09061013B2

反応ノート

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