Diisopropylethylamine → N-(4-{(1S,4S)-4-[3-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-1,2,3,4-tetrahydro-naphthalen-1-yloxy}-pyridin-2-yl)-2-methoxy-acetamide

HRID 630709Notes

Reaction equation

HRID 630709 reaction equation
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@@H:5]([O:12][C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20](=[O:24])[CH2:21][O:22][CH3:23])[CH:14]=2)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.ClC(Cl)(Cl)C[O:37][C:38](=O)[NH:39][C:40]1[N:41]([C:49]2[CH:54]=[CH:53][C:52]([CH3:55])=[CH:51][CH:50]=2)[N:42]=[C:43]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH:44]=1>O1CCOCC1>[C:45]([C:43]1[CH:44]=[C:40]([NH:39][C:38](=[O:37])[NH:1][C@@H:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C@@H:5]([O:12][C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20](=[O:24])[CH2:21][O:22][CH3:23])[CH:14]=3)[CH2:4][CH2:3]2)[N:41]([C:49]2[CH:54]=[CH:53][C:52]([CH3:55])=[CH:51][CH:50]=2)[N:42]=1)([CH3:48])([CH3:46])[CH3:47]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 86686966N-[4-((1S,4S)-4-Amino-1,2,3,4-tetrahydro-naphthalen-1-yloxy)-pyridin-2-yl]-2-methoxy-acetamide

Product 1

HCID 86686967N-(4-{(1S,4S)-4-[3-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-1,2,3,4-tetrahydro-naphthalen-1-yloxy}-pyridin-2-yl)-2-methoxy-acetamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Intermediate 10d (204 mg, 0.62 mmol) and DIPEA (0.127 mL, 0.80 mmol) in 1,4-dioxane (6 mL), (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; 315 mg, 0.78 mmol) was added. The mixture was heated at 80° C. under argon for 17 h, and then evaporated to dryness. The residue was purified by FCC, eluting with 0-100% ethyl acetate in cyclohexane, to give the slightly impure product (0.262 g). Further purification by HPLC (Method 6) gave the title compound as a white solid (102 mg, 28%). LCMS (Method 5): Rt 4.51 min, m/z 583 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.26 (9H, s), 1.69-1.81 (1H, m), 1.90-2.24 (3H, m), 2.36 (3H, s), 3.36 (3H, s), 4.05 (2H, s), 4.86-4.94 (1H, m), 5.62-5.67 (1H, m), 6.32 (1H, s), 6.91 (1H, dd, J 2.5, 5.9), 7.03 (1H, d, J 8.4), 7.26-7.37 (8H, m), 7.60 (1H, br d, J 2.0), 8.01 (1H, s), 8.16 (1H, d, J 5.7), 9.90 (1H, s).

Workup

  1. addition315 mg, 0.78 mmol) was added
  2. customevaporated to dryness
  3. customThe residue was purified by FCC
  4. washeluting with 0-100% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-43395582edc74cbc8765d82e351d5b2f
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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