Dimethylamine → 1-[5-tert-Butyl-2-(2-dimethylamino-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 75615Notes

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]([C:34]5[C:39]([Cl:40])=[CH:38][CH:37]=[CH:36][C:35]=5[Cl:41])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([CH2:42][CH2:43]OS(C)(=O)=O)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:49][NH:50][CH3:51]>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]([C:34]5[C:39]([Cl:40])=[CH:38][CH:37]=[CH:36][C:35]=5[Cl:41])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([CH2:42][CH2:43][N:50]([CH3:51])[CH3:49])[N:6]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of Intermediate 28a (110 mg, 0.15 mmol) and dimethylamine (2.0M in THF, 1.54 mL, 3.09 mmol) in anhydrous THF (2 mL) was stirred at 60° C. for 18 h in a sealed vial. The volatiles were concentrated in vacuo and the resultant residue was purified by MDAP (Method 7) to afford the title compound (44 mg, 43%). LCMS (Method 5): Rt 3.50 min, m/z 661 [MH+]. 1H NMR (400 MHz, DMSO): 1.19 (9H, s), 1.83-2.14 (4H, m), 2.18 (6H, s), 2.59 (2H, t, J=6.9 Hz), 3.96 (2H, t, J=6.9 Hz), 4.79-4.87 (1H, m), 5.53 (1H, t, J=4.0 Hz), 6.01 (1H, s), 6.92 (1H, d, J=8.7 Hz), 7.22-7.28 (1H, m), 7.30-7.38 (4H, m), 7.68-7.78 (3H, m), 7.90 (1H, dd, J=9.9, 0.8 Hz), 7.96 (1H, d, J=2.0 Hz), 8.15 (1H, s), 8.44 (1H, s).

Workup

concentrationThe volatiles were concentrated in vacuo
customthe resultant residue was purified by MDAP (Method 7)

Sources & evidence

ORD record: ord-4116978cbef94f75b9ed8fe681446399
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835431B2

Reaction notes

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