Formic Acid → HCID 117665878、化合物

HRID 630696ノート

反応式

HRID 630696 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][C:10]2[N:14]3[CH:15]=[C:16]([O:19][C@H:20]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[C@@H:23]([NH2:30])[CH2:22][CH2:21]4)[CH:17]=[CH:18][C:13]3=[N:12][N:11]=2)[CH2:4][CH2:3]1.ClC(Cl)(Cl)C[O:34][C:35](=[O:53])[NH:36][C:37]1[N:38]([C:46]2[CH:51]=[CH:50][C:49]([CH3:52])=[CH:48][CH:47]=2)[N:39]=[C:40]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:41]=1.CCN(C(C)C)C(C)C.C(O)=O>O1CCOCC1>[CH:35]([OH:53])=[O:34].[C:42]([C:40]1[CH:41]=[C:37]([NH:36][C:35]([NH:30][C@@H:23]2[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:20]([O:19][C:16]3[CH:17]=[CH:18][C:13]4[N:14]([C:10]([CH2:9][CH2:8][N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[N:11][N:12]=4)[CH:15]=3)[CH2:21][CH2:22]2)=[O:34])[N:38]([C:46]2[CH:51]=[CH:50][C:49]([CH3:52])=[CH:48][CH:47]=2)[N:39]=1)([CH3:45])([CH3:43])[CH3:44]

参加物

6

反応物 4

HCID 284Formic AcidHCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 86686949HCID 86686949、化合物

生成物 1

HCID 117665878HCID 117665878、化合物

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
60 °C

実験手順

Intermediate 2c (85.0 mg, 0.21 mmol) was dissolved in 1,4-dioxane (2 mL) and (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (Synthetic Communications, 2009, 39, 3999-4009, which is incorporated herein by reference in its entirety; 96.0 mg, 0.24 mmol) and DIPEA (75.0 μl, 0.43 mmol) were added. The reaction was heated to 60° C. for 18 h. After cooling, the mixture was partitioned between EtOAc (50 mL) and water (50 mL), and extracted into EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4) and evaporated in vacuo. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, then further purified by HPLC (C, 18 X-select column, 10-40% MeCN in H2O, 0.1% formic acid) to give the title compound mainly as formic acid salt (43.0 mg, 0.065 mmol, 31%). LCMS (Method 5) Rt 3.54 mins, m/z 662 [MH+]. 1H NMR (400 MHz, d4-MeOD): 1.30 (9H, s), 1.90-2.05 (2H, m), 2.06-2.15 (1H, m), 2.20-2.30 (1H, m), 2.38 (3H, s), 2.40 (3H, s), 2.55-2.75 (8H, br s), 2.90-2.95 (2H, t, J 7.4), 3.29-3.32 (2H, t, J 7.4), 4.86-4.92 (1H, dd, J 8.8, 5.6), 5.43-5.47 (1H, t, J 4.2), 6.33 (1H, s), 7.21-7.35 (11H, m), 7.60-7.64 (1H, d, J 9.9), 8.07-8.09 (1H, d, J 1.9), 8.40-8.50 (0.4H, br s, formate).

後処理

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between EtOAc (50 mL) and water (50 mL)
  3. extractionextracted into EtOAc (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by FCC
  8. customfurther purified by HPLC (C, 18 X-select column, 10-40% MeCN in H2O, 0.1% formic acid)

出典と根拠

ORDレコード
ord-67dcba1ad05143cf8984eb0acf729f2c
出典データセット
uspto-grants-2016_04
特許番号
US09315503B2

反応ノート

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