Formic Acid → HCID 86686974, compound

HRID 1402109Notes

Reaction equation

HRID 1402109 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[N:13]3[CH:14]=[C:15]([O:18][C@H:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[C@@H:22]([NH2:29])[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:4][CH2:3]1.ClC(Cl)(Cl)C[O:33][C:34](=[O:52])[NH:35][C:36]1[N:37]([C:45]2[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=2)[N:38]=[C:39]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH:40]=1.C(N(C(C)C)CC)(C)C.C(O)=O>O1CCOCC1>[CH:34]([OH:52])=[O:33].[C:41]([C:39]1[CH:40]=[C:36]([NH:35][C:34]([NH:29][C@@H:22]2[C:23]3[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=3)[C@H:19]([O:18][C:15]3[CH:16]=[CH:17][C:12]4[N:13]([C:9]([CH2:8][N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[N:10][N:11]=4)[CH:14]=3)[CH2:20][CH2:21]2)=[O:33])[N:37]([C:45]2[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=2)[N:38]=1)([CH3:44])([CH3:42])[CH3:43]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 86686973HCID 86686973, compound

Product 1

HCID 86686974HCID 86686974, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

Intermediate 14c (120 mg, 0.31 mmol) was dissolved in 1,4-dioxane (2.0 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; 124 mg, 0.31 mmol) and diisopropylethylamine (106 μL, 0.61 mmol) were added. The reaction was heated to 60° C. for 20 h. After cooling, the mixture was partitioned between EtOAc (50 mL) and water (50 mL), and extracted into EtOAc (3 x). 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 (C18X-select column, 20-70% MeCN in H2O, 0.1% formic acid) to give the title compound as the formic acid salt (103 mg, 0.16 mmol, 52%). LCMS (Method 5): Rt 3.63 min, m/z=648 [MH+]. 1H NMR (400 MHz, d4-MeOD): 1.30 (9H, s), 1.90-1.99 (1H, m), 1.99-2.07 (1H, m), 2.10-2.19 (1H, m), 2.21-2.30 (1H, m), 2.37 (3H, s), 2.38 (3H, s), 2.52-2.67 (8H, br s), 4.05-4.09 (1H, d, J=14.3 Hz), 4.11-4.15 (1H, d, J=14.3 Hz), 4.88-4.93 (1H, dd, J 8.9, 5.6 Hz), 5.41-5.44 (1H, t, J=4.3 Hz), 6.33 (1H, s), 7.22-7.36 (11H, m), 7.63-7.67 (1H, d, J=10.0 Hz), 8.21-8.22 (1H, d, J=1.9 Hz), 8.44-8.45 (0.25H, s).

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between EtOAc (50 mL) and water (50 mL)
  3. extractionextracted into EtOAc (3 x)
  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 (C18X-select column, 20-70% MeCN in H2O, 0.1% formic acid)

Sources & evidence

ORD record
ord-c3db4c1f894e417e819401c4bf707f00
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

Loading…