Diisopropylethylamine → 1-{(1S,4R)-4-[3-(4-Allyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-[5-tert-butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-urea

HRID 630775Notes

Reaction equation

HRID 630775 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]([CH2:22][OH:23])=[CH:18][CH:17]=2)[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH2:27]([O:30][CH:31]1[CH2:36][CH2:35][N:34]([C:37]2[N:41]3[CH:42]=[C:43]([O:46][C@H:47]4[C:56]5[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=5)[C@@H:50]([NH2:57])[CH2:49][CH2:48]4)[CH:44]=[CH:45][C:40]3=[N:39][N:38]=2)[CH2:33][CH2:32]1)[CH:28]=[CH2:29].CCN(C(C)C)C(C)C>O1CCOCC1>[CH2:27]([O:30][CH:31]1[CH2:36][CH2:35][N:34]([C:37]2[N:41]3[CH:42]=[C:43]([O:46][C@H:47]4[C:56]5[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=5)[C@@H:50]([NH:57][C:5]([NH:6][C:7]5[N:8]([C:16]6[CH:21]=[CH:20][C:19]([CH2:22][OH:23])=[CH:18][CH:17]=6)[N:9]=[C:10]([C:12]([CH3:14])([CH3:15])[CH3:13])[CH:11]=5)=[O:24])[CH2:49][CH2:48]4)[CH:44]=[CH:45][C:40]3=[N:39][N:38]=2)[CH2:33][CH2:32]1)[CH:28]=[CH2:29]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86687059(1S,4R)-4-[3-(4-Allyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineHCID 89612285[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 866870611-{(1S,4R)-4-[3-(4-Allyloxy-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-[5-tert-butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-ureaYield 65%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A yellow-brown solution of Intermediate 33a (99.6 mg, 0.237 mmol), Intermediate 57b (90.3 mg, 0.215 mmol) and DIPEA (0.047 mL, 0.269 mmol) in dioxane (3 mL) was stirred at 60° C. for 18 h. The solution was concentrated in vacuo, then the residue 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. The residue was purified by FCC, using 2-8% [2M NH3 in MeOH] in DCM, to give the title compound as a pale yellow solid (96.4 mg, 65%). LCMS (Method 3): Rt 3.54 min, m/z 691 [MH+].

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. extractionextracted with DCM (2×5 mL)
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-19599cf2f42c4ffba2f5c26349239b06
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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