Diisopropylethylamine → 3-(5-cyano-4-(3-(4-fluorophenoxy)azetidin-1-yl)pyrimidin-2-ylamino)-N-methylbenzamide

HRID 522897Notes

Reaction equation

HRID 522897 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=2)[C:12]([NH:14][CH3:15])=[O:13])[C:5]([C:19]#[N:20])=[CH:4][N:3]=1.Cl[C:22]1[C:27]([C:28]#[N:29])=[CH:26][N:25]=[C:24]([NH:30][C:31]2[CH:32]=[C:33]([CH:38]=[CH:39][CH:40]=2)[C:34]([NH:36][CH3:37])=[O:35])[N:23]=1.Cl.[F:42][C:43]1[CH:53]=[CH:52][C:46]([O:47][CH:48]2[CH2:51][NH:50][CH2:49]2)=[CH:45][CH:44]=1.C(N(CC)C(C)C)(C)C>CC(O)C>[C:28]([C:27]1[C:22]([N:50]2[CH2:51][CH:48]([O:47][C:46]3[CH:45]=[CH:44][C:43]([F:42])=[CH:53][CH:52]=3)[CH2:49]2)=[N:23][C:24]([NH:30][C:31]2[CH:32]=[C:33]([CH:38]=[CH:39][CH:40]=2)[C:34]([NH:36][CH3:37])=[O:35])=[N:25][CH:26]=1)#[N:29].[C:19]([C:5]1[C:6]([NH:8][C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][CH:18]=2)[C:12]([NH:14][CH3:15])=[O:13])=[N:7][C:2]([N:50]2[CH2:51][CH:48]([O:47][C:46]3[CH:45]=[CH:44][C:43]([F:42])=[CH:53][CH:52]=3)[CH2:49]2)=[N:3][CH:4]=1)#[N:20]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 214287323-(4-Fluorophenoxy)azetidine hydrochlorideHCID 86685250HCID 86685250, compoundHCID 86685251HCID 86685251, compound

Product 2

HCID 673543503-(5-cyano-4-(3-(4-fluorophenoxy)azetidin-1-yl)pyrimidin-2-ylamino)-N-methylbenzamideHCID 67354915HCID 67354915, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
84 °C

Procedure

To the reaction mixture of 3-(2-chloro-5-cyanopyrimidin-4-ylamino)-N-methylbenzamide and 3-(4-chloro-5-cyanopyrimidin-2-ylamino)-N-methylbenzamide (172.7 mg, 0.600 mmol) and 3-(4-fluorophenoxy)azetidine hydrochloride (128 mg, 0.631 mmol) in a disposable sealed tube at RT was added 2-propanol (4 mL) followed by N,N-diisopropylethylamine (0.314 mL, 1.802 mmol). The resulting reaction mixture was heated to 84° C. for 4.5 h, cooled to RT, concentrated, adsorbed onto silica gel, purified using MPLC (25 g cartridge about 20% full, 40 g column, 0 to 80% 90/10 CH2Cl2-MeOH in CH2Cl2) giving 3-(5-cyano-4-(3-(4-fluorophenoxy)azetidin-1-yl)pyrimidin-2-ylamino)-N-methylbenzamide (19.3 mg) and 3-(5-cyano-2-(3-(4-fluorophenoxy)azetidin-1-yl)pyrimidin-4-ylamino)-N-methylbenzamide (13.2 mg).

Workup

  1. customThe resulting reaction mixture
  2. temperaturecooled to RT
  3. concentrationconcentrated
  4. custompurified

Sources & evidence

ORD record
ord-7ab60c6b16e743649613f722c4759ce7
Source dataset
uspto-grants-2016_05
Patent number
US09334269B2

Reaction notes

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