Dichloromethane → (S)-4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)aniline hydrochloride

HRID 707453Notes

Reaction equation

HRID 707453 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[S:14]([CH3:17])(=[O:16])=[O:15])[N:5]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@@H:19]2[CH3:24])[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][C:36]([NH:39]C(=O)OC(C)(C)C)=[CH:35][CH:34]=2)O1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[ClH:1].[CH3:24][C@@H:19]1[N:18]([C:4]2[N:5]=[C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[S:14]([CH3:17])(=[O:16])=[O:15])[N:7]=[C:2]([C:33]3[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=3)[N:3]=2)[CH2:23][CH2:22][O:21][CH2:20]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 2734617tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamateHCID 89463997(S)-4-(4-chloro-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)-3-methylmorpholine

Product 1

HCID 117761400(S)-4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)aniline hydrochlorideYield 57%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (S)-4-(4-chloro-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)-3-methylmorpholine (step (ii) Example 1) (1 g, 2.7 mmol) in 1,4-dioxane (16 ml) was added tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (1 eq), Pd(dppf)Cl2.DCM (0.05 eq) and 2M aqueous Na2CO3. The reaction was heated in the microwave at 120° C. for 40 minutes. The reaction was concentrated in vacuo and the residue partitioned between saturated NaHCO3 and DCM. The aqueous phase was extracted three times into DCM, the organic extracts were combined, dried over magnesium sulphate and concentrated in vacuo. The residue was purified by flash chromatography on a Nh-KP column, eluting with 0-100% EtOAc in petroleum ether. The compound was deprotected by stirring in MeOH (10 ml) with 4M HCl in 1,4-dioxane (5 ml) for 24 hrs to give (S)-4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)aniline hydrochloride, 716 mg, 57% yield.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe residue partitioned between saturated NaHCO3 and DCM
  3. extractionThe aqueous phase was extracted three times into DCM
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on a Nh-KP column
  7. washeluting with 0-100% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-01ce2189500f4fcc8e78e86f20c49c2e
Source dataset
uspto-grants-2015_11
Patent number
US09175011B2

Reaction notes

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