Sodium Carbonate → 5-(6-((Methyl(1-methylpiperidin-4-yl)amino)methyl)-4-morpholinothieno[2,3-d]pyrimidin-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine

HRID 391035Notes

Reaction equation

HRID 391035 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[CH:10]=[C:9]([CH2:11][N:12]([CH3:20])[CH:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)[S:8][C:6]=2[N:7]=1.C([O-])([O-])=O.[Na+].[Na+].CC1(C)C(C)(C)OB([C:41]2[C:42]([C:48]([F:51])([F:50])[F:49])=[N:43][C:44]([NH2:47])=[N:45][CH:46]=2)O1>CC#N.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH3:20][N:12]([CH2:11][C:9]1[S:8][C:6]2[N:7]=[C:2]([C:41]3[C:42]([C:48]([F:51])([F:50])[F:49])=[N:43][C:44]([NH2:47])=[N:45][CH:46]=3)[N:3]=[C:4]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[C:5]=2[CH:10]=1)[CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 574164395-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyrimidin-2-amineHCID 86623517N-((2-chloro-4-morpholinothieno[2,3-d]pyrimidin-6-yl)methyl)-N,1-dimethylpiperidin-4-amine

Product 1

HCID 582338545-(6-((Methyl(1-methylpiperidin-4-yl)amino)methyl)-4-morpholinothieno[2,3-d]pyrimidin-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

(2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-methyl-(1-methyl-piperidin-4-yl)-amine (100 mg), 1M Na2CO3 (0.7 mL), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-trifluoromethyl-pyrimidin-2-ylamin (1.5 eq.) [WO 2007/084786] and bis(triphenylphosphine)palladium (II) chloride (0.05 eq.) in MeCN (15 mL) was heated at 140° C. for 25 min. in microwave. The resulting mixture was diluted with water then extracted with ethyl acetate. Combined extracts were dried (Na2SO4), filtered and concentrated then purified by preparative HPLC to give 321 (45 mg). NMR: (CDCl3): 1.2 (s, 2H, CH2), 1.57-1.65 (m, 2H, CH2), 1.72-1.74 (m, 2H, CH2), 1.87-1.92 (m, 2H, CH2), 2.21 (s, 3H, CH3), 2.26 (s, 3H, CH3), 2.54 (m, H, CH), 2.85-2.87 (m, 2H, CH2), 3.76-3.78 (m, 4H, 2×CH2), 3.84-3.86 (m, 4H, 2×CH2), 5.34 (sbr, 2H, NH2), 7.06 (s, H, ArH), 8.91 (s, H, ArH). MS: (ESI+): MH+=523.35

Workup

  1. extractionthen extracted with ethyl acetate
  2. dry with materialCombined extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customthen purified by preparative HPLC

Sources & evidence

ORD record
ord-27d6bef192764a1f8482f2d4f7860462
Source dataset
uspto-grants-2013_02
Patent number
US08383620B2

Reaction notes

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