Water → 5-(8,8-Dimethyl-1-morpholin-4-yl-5,8-dihydro-6H-7-oxa-9-thia-2,4-diaza-fluoren-3-yl)-pyrimidin-2-ylamine

HRID 334156Notes

Reaction equation

HRID 334156 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:5]2[S:6][C:7]3[C:8]([CH3:16])([CH3:15])[O:9][CH2:10][CH2:11][C:12]=3[C:13]=2[N:14]=1.C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].O.CC1(C)C(C)(C)OC([C:41]2[CH:42]=[N:43][C:44]([NH2:47])=[N:45][CH:46]=2)O1>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:15][C:8]1([CH3:16])[C:7]2[S:6][C:5]3[C:4]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[N:3][C:2]([C:41]4[CH:42]=[N:43][C:44]([NH2:47])=[N:45][CH:46]=4)=[N:14][C:13]=3[C:12]=2[CH2:11][CH2:10][O:9]1

Participants

7

Reactant 5

HCID 962WaterHCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 679759095-(4,4,5,5-Tetramethyl-1,3-dioxolan-2-yl)pyrimidin-2-amineHCID 706766073-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,8-dihydro-6H-7-oxa-9-thia-2,4-diaza-fluorene

Product 1

HCID 573876505-(8,8-Dimethyl-1-morpholin-4-yl-5,8-dihydro-6H-7-oxa-9-thia-2,4-diaza-fluoren-3-yl)-pyrimidin-2-ylamineYield 22.6%

Reagents, catalysts & solvents 1

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)Catalyst

Procedure

3-Chloro-8,8-dimethyl-1-morpholin-4-yl-5,8-dihydro-6H-7-oxa-9-thia-2,4-diaza-fluorene (10 mg, 0.03 mmol) was dissolved in acetonitrile (2 mL, 40 mmol) and added 1 M sodium carbonate in water (2 mL, 2 mmol), 5-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)pyrimidin-2-amine (9.0 mg, 0.041 mmol), and Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.1 mg, 0.001 6 mmol). The reaction was placed on the Biotage microwave at 120° C. for 15 minutes. The aqueous layer was pipetted off and the organic layer was concentrated in vacuo and was purified by silica gel chromatography (0 to 100% ethyl acetate/heptanes) on the CombiFlash® Rf system using a basic alumina column and concentrated in vacuo to give (85% pure) 168 (2.7 mg, 20% yield). M+1: 399.3. 1H NMR (400 MHz, CDCl3) δ 9.30 (s, 2H), 5.34 (brs, 2H), 4.08 (t, 2H), 4.01 (m, 4H), 3.87 (m, 4H), 2.95 (t, 2H), 1.62 (s, 6H)

Workup

  1. concentrationthe organic layer was concentrated in vacuo
  2. customwas purified by silica gel chromatography (0 to 100% ethyl acetate/heptanes) on the CombiFlash® Rf system
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-95fe2f27ac7c44818e11bc1cd62d1432
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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