Diisopropylethylamine → 1-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-(2,6-dichloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

HRID 75614Notes

Reaction equation

HRID 75614 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:19])[NH:6][C:7]1[N:8]([CH2:16][CH2:17][OH:18])[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=1[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.CCN(C(C)C)C(C)C>O1CCOCC1>[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]([C:24]5[C:23]([Cl:22])=[CH:28][CH:27]=[CH:26][C:25]=5[Cl:29])=[N:31][N:32]=4)[CH:35]=3)[CH2:41][CH2:42]2)=[O:19])[N:8]([CH2:16][CH2:17][OH:18])[N:9]=1)([CH3:13])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86686715(1S,4R)-4-[3-(2,6-Dichloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineHCID 86686717[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 866867161-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-(2,6-dichloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaYield 14.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of Intermediate 26a (100 mg, 0.279 mmol), Intermediate 26d (108 mg, 0.254 mmol), and DIPEA (73 μL, 0.419 mmol) in dioxane (2.5 mL) was stirred at 60° C. for 42 h and then left standing at RT for 72 h. The volatiles were concentrated in vacuo and the resultant residue was purified by FCC, using 0-10% MeOH in DCM followed by MDAP (Method 7) to afford the title compound (23 mg, 14%) as a white solid. LCMS (Method 5): Rt 4.19 min, m/z 634 [MH+]. 1H NMR (400 MHz, DMSO): 1.21 (9H, s), 1.79-2.16 (4H, m), 3.62-3.70 (2H, m), 3.94 (2H, t, J=6.0 Hz), 4.78-4.88 (1H, m), 4.99 (1H, br s), 5.55 (1H, t, J=4.2 Hz), 6.05 (1H, s), 7.07 (1H, d, J=8.6 Hz), 7.23-7.30 (1H, m), 7.31-7.38 (4H, m), 7.70-7.74 (1H, m), 7.74-7.80 (2H, m), 7.91 (1H, d, J=9.9 Hz), 7.98 (1H, d, J=2.1 Hz), 8.19 (1H, s).

Workup

  1. waitleft
  2. waitstanding at RT for 72 h
  3. concentrationThe volatiles were concentrated in vacuo
  4. customthe resultant residue was purified by FCC

Sources & evidence

ORD record
ord-6bc6444d46bb40a68845446851ee69cd
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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