Isopropanol → Ammonia methanol dichloromethane

HRID 2355080Notes

Reaction equation

HRID 2355080 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:12]=[C:13]([NH:18][C:19](=[O:31])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[C:21]=3[CH3:30])[CH:14]=[CH:15][C:16]=2[CH3:17])=[O:10])=[CH:4][N:3]=1.[N:32]1[CH:37]=[CH:36][CH:35]=[C:34](CN)[CH:33]=1.CC(O)C.C[CH2:45][N:46](C(C)C)C(C)C.[CH2:53]([Cl:55])[Cl:54]>>[CH2:53]([Cl:55])[Cl:54].[CH3:9][OH:10].[NH3:3].[CH3:30][C:21]1[C:22]([C:26]([F:29])([F:28])[F:27])=[CH:23][CH:24]=[CH:25][C:20]=1[C:19]([NH:18][C:13]1[CH:14]=[CH:15][C:16]([CH3:17])=[C:11]([C:9]([NH:8][C:5]2[CH:4]=[N:3][C:2]([NH:46][CH2:45][C:37]3[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=3)=[N:7][CH:6]=2)=[O:10])[CH:12]=1)=[O:31]

Participants

7

Reactant 5

HCID 3776IsopropanolHCID 6344DichloromethaneHCID 310183-PyridinemethanamineHCID 81531DiisopropylethylamineHCID 59381868HCID 59381868, compound

Product 2

HCID 21584172Ammonia methanol dichloromethaneHCID 59381871HCID 59381871, compound

Conditions

Temperature
140 °C

Procedure

A small microwave reaction vessel was charged with N-(3-(((2-chloro-5-pyrimidinyl)amino)carbonyl)-4-methylphenyl)-2-methyl-3-(trifluoromethyl)benzamide 19 (0.100 g, 0.22 mmol), pyridin-3-ylmethanamine (0.091 ml, 0.89 mmol) and IPA (1 mL). DIEA (0.058 ml, 0.33 mmol) was added and the vessel was sealed. The reaction mixture was stirred and heated in a Smith Synthesizer® microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 140° C. for 30 min. After monitoring the reaction by LCMS and finding >95% conversion, the reaction was concentrated to dryness, and taken up in minimal CH2Cl2/MeOH. The crude reaction solution was injected onto the Isco {Redi-Sep® pre-packed silica gel column (40 g); eluent gradient: 3-80% 90/10/1 CH2Cl2/MeOH/NH3 in CH2Cl2 over 20 min} to afford pure 2-methyl-N-(4-methyl-3-(((2-((2-pyridinylmethyl)amino)-5-pyrimidinyl)amino)carbonyl)phenyl)-3-(trifluoromethyl)benzamide 21 as a white solid. MS m/z found 521.1 [MH+]; calc. for C27H23F3N6O2=520.18.

Workup

  1. customA small microwave reaction vessel
  2. customthe vessel was sealed
  3. customthe reaction by LCMS
  4. concentrationthe reaction was concentrated to dryness
  5. customThe crude reaction solution

Sources & evidence

ORD record
ord-d810d124d6f74334a2df52d7e2e958e1
Source dataset
uspto-grants-2010_07
Patent number
US07754717B2

Reaction notes

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