((S)-1-piperidin-4-yl-pyrrolidin-2-yl)-methanol dihydrochloride → [1-(4-Bromo-3-trifluoromethyl-phenyl)-5-methyl-3-pyrimidin-5-yl-1h-pyrazol-4-yl]-[4-((s)-2-hydroxymethyl-pyrrolidin-1-yl)-piperidin-1-yl]-methanone

HRID 1011992Notes

Reaction equation

HRID 1011992 reaction equation
CC1N(C2C=CC=C(C(F)(F)F)C=2)N=C(C2C=NC=NC=2)C=1C(O)=O.[Br:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[C:37]([CH3:38])=[C:36]([C:39]([OH:41])=O)[C:35]([C:42]3[CH:43]=[N:44][CH:45]=[N:46][CH:47]=3)=[N:34]2)=[CH:29][C:28]=1[C:48]([F:51])([F:50])[F:49].Cl.Cl.[NH:54]1[CH2:59][CH2:58][CH:57]([N:60]2[CH2:64][CH2:63][CH2:62][C@H:61]2[CH2:65][OH:66])[CH2:56][CH2:55]1>>[Br:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[C:37]([CH3:38])=[C:36]([C:39]([N:54]3[CH2:55][CH2:56][CH:57]([N:60]4[CH2:64][CH2:63][CH2:62][C@H:61]4[CH2:65][OH:66])[CH2:58][CH2:59]3)=[O:41])[C:35]([C:42]3[CH:47]=[N:46][CH:45]=[N:44][CH:43]=3)=[N:34]2)=[CH:29][C:28]=1[C:48]([F:51])([F:50])[F:49]

Participants

4

Reactant 3

HCID 66901571((S)-1-piperidin-4-yl-pyrrolidin-2-yl)-methanol dihydrochlorideHCID 673152105-methyl-3-pyrimidin-5-yl-1-(3-trifluoromethyl-phenyl)-1H-pyrazole-4-carboxylic acidHCID 673155081-(4-bromo-3-trifluoromethyl-phenyl)-5-methyl-3-pyrimidin-5-yl-1H-pyrazole-4-carboxylic acid

Product 1

HCID 57555021[1-(4-Bromo-3-trifluoromethyl-phenyl)-5-methyl-3-pyrimidin-5-yl-1h-pyrazol-4-yl]-[4-((s)-2-hydroxymethyl-pyrrolidin-1-yl)-piperidin-1-yl]-methanone

Procedure

In analogy to the procedure described in Example 160E], a mixture of 5-methyl-3-pyrimidin-5-yl-1-(3-trifluoromethyl-phenyl)-1H-pyrazole-4-carboxylic acid and 1-(4-bromo-3-trifluoromethyl-phenyl)-5-methyl-3-pyrimidin-5-yl-1H-pyrazole-4-carboxylic acid (example 173D]) and ((S)-1-piperidin-4-yl-pyrrolidin-2-yl)-methanoldihydrochloride (Example 161A]) gave a mixture of the title compound and example 175. Purification by reversed phase HPLC (MeCN:H2O) afforded [4-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-piperidin-1-yl]-[5-methyl-3-pyrimidin-5-yl-1-(3-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-methanone (Example 175) and [1-(4-bromo-3-trifluoromethyl-phenyl)-5-methyl-3-pyrimidin-5-yl-1H-pyrazol-4-yl]-[4-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-piperidin-1-yl]-methanone) as a white solid (31%). MS: 593.4 (1 Br, MH+).

Workup

  1. customgave

Sources & evidence

ORD record
ord-347d76d90efa4665802964f683570af1
Source dataset
uspto-grants-2011_07
Patent number
US07977358B2

Reaction notes

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