Water → 1-[5-tert-Butyl-2-(4-cyano-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4S)-4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

HRID 75593Notes

Reaction equation

HRID 75593 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:24])[NH:6][C:7]1[N:8]([C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH:27]([C:30]1[N:34]2[CH:35]=[C:36]([O:39][C@@H:40]3[C:49]4[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=4)[C@@H:43]([NH2:50])[CH2:42][CH2:41]3)[CH:37]=[CH:38][C:33]2=[N:32][N:31]=1)([CH3:29])[CH3:28].CCN(C(C)C)C(C)C.O>O1CCOCC1.CN(C=O)C.C(Cl)Cl.CO>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:50][C@@H:43]2[C:44]3[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=3)[C@@H:40]([O:39][C:36]3[CH:37]=[CH:38][C:33]4[N:34]([C:30]([CH:27]([CH3:29])[CH3:28])=[N:31][N:32]=4)[CH:35]=3)[CH2:41][CH2:42]2)=[O:24])[N:8]([C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)[N:9]=1)([CH3:14])([CH3:13])[CH3:15]

Participants

8

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 687825092,2,2-Trichloroethyl 3-tert-butyl-1-(4-cyanophenyl)-1H-pyrazol-5-ylcarbamateHCID 86686683(1S,4S)-4-(3-Isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Product 1

HCID 715985721-[5-tert-Butyl-2-(4-cyano-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4S)-4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 217120691,4-dioxane N,N-dimethylformamideSolvent

Procedure

A solution of Intermediate 14b (61.6 mg, 0.148 mmol), Intermediate 5c (43.4 mg, 0.135 mmol), and DIPEA (0.029 mL, 0.169 mmol) in dioxane-DMF (3:1, 2.0 mL) was stirred at 60° C. for 18 h. Water (3 mL) was added, then the mixture extracted with DCM-MeOH (9:1, 2×3 mL). The combined organics were passed through a hydrophobic frit and concentrated in vacuo to leave an orange oil. FCC, using 2-8% MeOH in DCM, gave the title compound as a white solid after freeze-drying (35.0 mg, 44%). LCMS (Method 5): Rt 4.46 min, m/z 589 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.28 (9H, s), 1.37 (3H, d, J 7.1), 1.39 (3H, d, J 7.1), 1.75 (1H, m), 2.01 (1H, m), 2.09-2.22 (2H, m), 3.57 (1H, sept, J 6.9), 4.88 (1H, m), 5.58 (1H, t, J 4.5), 6.38 (1H, s), 7.06 (1H, d, J 8.2), 7.23 (1H, dd, J 9.9, 2.2), 7.27 (1H, d, J 7.3), 7.29-7.38 (2H, m), 7.42 (1H, d, J 7.5), 7.69 (1H, dd, J 9.9, 0.9), 7.75 (2H, d, J 8.9), 7.96 (2H, d, J 8.7), 8.21 (2H, s).

Workup

  1. extractionthe mixture extracted with DCM-MeOH (9:1, 2×3 mL)
  2. concentrationconcentrated in vacuo
  3. customto leave an orange oil

Sources & evidence

ORD record
ord-e6a75c6ae34b4dcc859e511cc58e278d
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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