Methanol → HCID 86687107, compound

HRID 630821Notes

Reaction equation

HRID 630821 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:23])[NH:6][C:7]1[N:8]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH3:26][C@H:27]1[CH2:32][CH2:31][CH2:30][CH2:29][N:28]1[C:33]1[N:37]2[CH:38]=[C:39]([O:42][C@H:43]3[C:52]4[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=4)[C@@H:46]([NH2:53])[CH2:45][CH2:44]3)[CH:40]=[CH:41][C:36]2=[N:35][N:34]=1.CCN(C(C)C)C(C)C.CO>O1CCOCC1.C(Cl)Cl>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:53][C@@H:46]2[C:47]3[C:52](=[CH:51][CH:50]=[CH:49][CH:48]=3)[C@H:43]([O:42][C:39]3[CH:40]=[CH:41][C:36]4[N:37]([C:33]([N:28]5[CH2:29][CH2:30][CH2:31][CH2:32][C@@H:27]5[CH3:26])=[N:34][N:35]=4)[CH:38]=3)[CH2:44][CH2:45]2)=[O:23])[N:8]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[N:9]=1)([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 86687106(1S,4R)-4-[3-((S)-2-Methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Product 1

HCID 86687107HCID 86687107, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

An orange-brown solution of (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; 106 mg, 0.263 mmol), Intermediate 81d (94.4 mg, 0.250 mmol) and DIPEA (0.054 mL, 0.313 mmol) in dry dioxane (3 mL) was stirred at 70° C. for 16 h. The cooled solution was concentrated in vacuo, suspended in water (5 mL) and extracted with DCM (2×5 mL). The combined organics were passed through a hydrophobic fit and concentrated in vacuo to leave a brown gum. FCC, using 2-6% MeOH in DCM, gave a pale yellow solid (123 mg). Further purification by HPLC (XBridge C18 column, 40-90% MeCN in H2O, 0.1% NH4OH) gave the title compound as a white powder after freeze-drying (72.4 mg, 46%). LCMS (Method 5): Rt 5.04 min, m/z 633 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J 6.3), 1.27 (9H, s), 1.48-1.55 (2H, m), 1.63-1.71 (2H, m), 1.75-1.97 (4H, m), 2.00-2.16 (2H, m), 2.36 (3H, s), 2.90 (1H, ddd, J 12.1, 9.0, 3.9), 3.16 (1H, dt, J 12.1, 4.3), 3.29 (1H, m), 4.82 (1H, td, J 8.6, 5.5), 5.51 (1H, t, J 4.4), 6.32 (1H, s), 7.08 (1H, d, J 8.6), 7.19 (1H, dd, J 9.9, 2.2), 7.25-7.38 (8H, m), 7.64 (1H, dd, J 9.8, 0.8), 7.69 (1H, d, J 2.1), 8.04 (1H, s).

Workup

  1. concentrationThe cooled solution was concentrated in vacuo
  2. extractionextracted with DCM (2×5 mL)
  3. concentrationconcentrated in vacuo
  4. customto leave a brown gum

Sources & evidence

ORD record
ord-21e431a766b347eeb19447b2b81e6a59
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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