Dimethylamine → 1-{5-tert-Butyl-2-[4-chloro-3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1S,4R)-4-[3-((S)-2-methyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt

HRID 60688Notes

Reaction equation

HRID 60688 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[CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:39])=[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:54])=[C:44]([CH:53]=2)[O:45][CH2:46][CH2:47][O:48]S(C)(=O)=O)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:55][NH:56][CH3:57].C1C[O:61]CC1>>[CH:47]([OH:48])=[O:61].[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[CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:39])=[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:54])=[C:44]([O:45][CH2:46][CH2:47][N:56]([CH3:57])[CH3:55])[CH:53]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 117729585Methanesulfonic acid 2-{5-[3-tert-butyl-5-(3-{(1S,4R)-4-[3-((S)-2-methyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-pyrazol-1-yl]-2-chloro-phenoxy}-ethyl ester

Product 1

HCID 863429441-{5-tert-Butyl-2-[4-chloro-3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1S,4R)-4-[3-((S)-2-methyl-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate saltYield 38%

Procedure

A solution of Intermediate 78e (44 mg, 0.057 mmol) and dimethylamine (2M in THF, 0.57 mL, 1.14 mmol) in THF (1 mL) was heated at 60° C. for 18 h. The reaction mixture was cooled to RT and the solvent was removed under a stream of air, to leave a residue which was purified by MDAP (Method 7), to afford the title compound (16 mg, 38%). LCMS (Method 5): Rt: 3.42 min, m/z 726.5 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.10 (3H, d, J=6.2 Hz), 1.28 (9H, s), 1.54-1.65 (1H, m), 1.78-1.95 (3H, m), 1.95-2.08 (2H, m), 2.08-2.19 (2H, m), 2.21 (6H, s), 2.65 (2H, t, J=5.6 Hz), 3.09-3.16 (1H, m, obscured by water), 3.80-3.89 (1H, m), 4.06-4.14 (1H, m), 4.16 (2H, t, J=5.6 Hz), 4.75-4.84 (1H, m), 5.52 (1H, t, J=4.0 Hz), 6.34 (1H, s), 7.04-7.13 (3H, m), 7.22-7.39 (5H, m), 7.52-7.58 (2H, m), 7.79 (1H, d, J=1.9 Hz), 8.15-8.19 (2.2H, m).

Workup

  1. customthe solvent was removed under a stream of air
  2. customto leave a residue which
  3. customwas purified by MDAP (Method 7)

Sources & evidence

ORD record
ord-32233f049fd941f7bed33650e02795a8
Source dataset
uspto-grants-2016_09
Patent number
US09440974B2

Reaction notes

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