Morpholine → 1-{5-tert-Butyl-2-[4-chloro-3-(3-morpholin-4-yl-propoxy)-phenyl]-2H-pyrazol-3-yl}-3-[(1S,4R)-4-(3-piperidin-1-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

HRID 711209Notes

Reaction equation

HRID 711209 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]5)=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:40]2[CH:41]=[CH:42][C:43]([Cl:55])=[C:44]([CH:54]=2)[O:45][CH2:46][CH2:47][CH2:48]OS(C)(=O)=O)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[NH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]5)=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:40]2[CH:41]=[CH:42][C:43]([Cl:55])=[C:44]([O:45][CH2:46][CH2:47][CH2:48][N:65]3[CH2:70][CH2:69][O:68][CH2:67][CH2:66]3)[CH:54]=2)[N:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 117729580HCID 117729580, compound

Product 1

HCID 863431361-{5-tert-Butyl-2-[4-chloro-3-(3-morpholin-4-yl-propoxy)-phenyl]-2H-pyrazol-3-yl}-3-[(1S,4R)-4-(3-piperidin-1-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-ureaYield 34.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A solution of Intermediate 76a (214 mg, 0.27 mmol) and DIPEA (95 μL, 0.54 mmol) in THF (5 mL) was treated with morpholine (47 μL, 0.54 mmol). The mixture was stirred at 50° C. for 18 h in a sealed vial. The volatiles were concentrated in vacuo and the product was purified by MDAP purification (Method 7) to give the title compound (72 mg, 34%). LCMS (Method 5): Rt 3.60 min, m/z 782.6 [MH+].+]. 1H NMR (400 MHz, d6-DMSO): 1.28 (9H, s), 1.57-1.65 (2H, m), 1.68-1.77 (4H, m), 1.80-1.94 (4H, m), 1.99-2.17 (2H, m), 2.24-2.32 (3H, bs), 2.36-2.42 (2H, t, J=6.9), 3.11-3.17 (4H, m), 3.48-3.52 (4H, m), 4.09-4-15 (2H, t, J=6.52 Hz), 4.76-4.84 (1H, m), 5.54 (1H, t, J=4.3 Hz), 6.34 (1H, s), 7.03-7.11 (2H, m), 7.16 (1H, dd, J=2.0, 9.9 Hz), 7.21-7.41 (5H, m), 7.54 (1H, d, J=8.5 Hz), 7.59-7.65 (2H, m), 8.14 (1H, br s).

Workup

  1. concentrationThe volatiles were concentrated in vacuo
  2. customthe product was purified by MDAP purification (Method 7)

Sources & evidence

ORD record
ord-e404db6845a74bdd9687761562b4301f
Source dataset
uspto-grants-2015_11
Patent number
US09181242B2

Reaction notes

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