Formic Acid → HCID 117665878, compound

HRID 630696Notes

Reaction equation

HRID 630696 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

HCID 117665878HCID 117665878, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-67dcba1ad05143cf8984eb0acf729f2c
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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