5-(Aminomethyl)-4-(2-fluoro-2-propyl)pyrimidine Dihydrochloride → (1S,3R)-3-((2-(((4-(2-Fluoropropan-2-yl)pyrimidin-5-yl)methyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)-2,2-dimethylcyclobutanol

HRID 1749417Notes

Reaction equation

HRID 1749417 reaction equation
[CH3:1][C:2]1([CH3:22])[C@H:5]([NH:6][C:7]2[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][N:10]=[C:9](S(C)(=O)=O)[N:8]=2)[CH2:4][C@@H:3]1[OH:21].Cl.Cl.[F:25][C:26]([C:29]1[C:34]([CH2:35][NH2:36])=[CH:33][N:32]=[CH:31][N:30]=1)([CH3:28])[CH3:27]>O1CCOCC1>[F:25][C:26]([C:29]1[C:34]([CH2:35][NH:36][C:9]2[N:8]=[C:7]([NH:6][C@@H:5]3[CH2:4][C@H:3]([OH:21])[C:2]3([CH3:22])[CH3:1])[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][N:10]=2)=[CH:33][N:32]=[CH:31][N:30]=1)([CH3:27])[CH3:28]

Participants

4

Reactant 2

HCID 862229165-(Aminomethyl)-4-(2-fluoro-2-propyl)pyrimidine DihydrochlorideHCID 118162086(1S,3R)-2,2-dimethyl-3-((2-(methylsulfonyl)-5-(trifluoromethyl)pyrimidin-4-yl)amino)cyclobutanol

Product 1

HCID 118162241(1S,3R)-3-((2-(((4-(2-Fluoropropan-2-yl)pyrimidin-5-yl)methyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)-2,2-dimethylcyclobutanolYield 50.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of (1S,3R)-2,2-Dimethyl-3-((2-(methylsulfonyl)-5-(trifluoromethyl)pyrimidin-4-yl)amino)cyclobutanol (1.0 equiv.) and (4-(2-fluoropropan-2-yl)pyrimidin-5-yl)methanamine dihydrochloride (1.3 equiv.) were combined in dioxane (0.4 M) and stirred at ambient temperature. After 1 h, the solution was heated to 75° C. After 16 h, the solution was concentrated under reduced pressure and after standard work-up the title compound (50.9% yield) was obtained. The absolute stereochemistry was determined, using the chiral intermediate, as described herein for other compounds. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 9.01 (s, 1H), 8.47-8.67 (m, 1H), 7.94-8.14 (m, 1H), 7.78 (br. s., 1H), 6.07 (d, J=7.81 Hz, 1H), 4.66-4.91 (m, 2H), 3.35 (br. s., 1H), 1.96-2.22 (m, 1H), 1.62-1.82 (m, 6H), 0.54-1.23 (m, 6H); MS(ESI) m/z 429.3[M+1]+.

Workup

  1. temperaturethe solution was heated to 75° C
  2. waitAfter 16 h
  3. concentrationthe solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6286111c6f904150a875aa94941a7043
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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