1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → N2-[4-(dimethylphosphoryl)-2-methoxyphenyl]-N4-[2-(propan-2-ylsulfonyl)phenyl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine

HRID 1471988Notes

Reaction equation

HRID 1471988 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[S:26]([CH:29]([CH3:31])[CH3:30])(=[O:28])=[O:27])[C:5]2[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:6]=2[N:7]=1.Cl.[CH3:33][P:34]([C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[C:39]([O:44][CH3:45])[CH:38]=1)([CH3:36])=[O:35].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(O[Na])(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:36][P:34]([C:37]1[CH:43]=[CH:42][C:40]([NH:41][C:2]2[N:3]=[C:4]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[S:26]([CH:29]([CH3:31])[CH3:30])(=[O:28])=[O:27])[C:5]3[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:17])([CH3:18])[CH3:16])[C:6]=3[N:7]=2)=[C:39]([O:44][CH3:45])[CH:38]=1)([CH3:33])=[O:35]

Participants

6

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 681571314-(Dimethylphosphoryl)-2-methoxyaniline hydrochlorideHCID 866687932-chloro-N-[2-(propan-2-ylsulfonyl)phenyl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-amineHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 86668794N2-[4-(dimethylphosphoryl)-2-methoxyphenyl]-N4-[2-(propan-2-ylsulfonyl)phenyl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamineYield 54%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

To a microwave reaction tube was charged with 2-chloro-N-[2-(propan-2-ylsulfonyl)phenyl]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine (180 mg, 0.374 mmol), 4-(dimethylphosphoryl)-2-methoxyaniline hydrochloride (105 mg, 0.45 mmol), Pd2(dba)3 (34 mg, 0.0374 mmol), Xanthphos (26 mg, 0.045 mmol), and t-BuONa (129 mg, 1.346 mmol). This mixture was degassed via 3-cycle of vacuum and re-fill with N2. Anhydrous 1,4-dioxane (2 mL from sure-seal bottle) was added and the reaction was then run under microwave irradiation at 140° C. for 20 min. Water and EtOAc was added to facilitate extraction. Chromatography on silica gel (10% MeOH in CH2Cl2 as eluent) gave the desired product in 54% yield (130 mg). MS/ES+: m/z=644.

Workup

  1. customTo a microwave reaction tube
  2. customThis mixture was degassed via 3-cycle of vacuum and re-fill with N2
  3. additionAnhydrous 1,4-dioxane (2 mL from sure-seal bottle) was added
  4. customthe reaction was then run under microwave irradiation at 140° C. for 20 min
  5. additionWater and EtOAc was added
  6. extractionextraction

Sources & evidence

ORD record
ord-aa32cea4b9994668aa168162c4dbe939
Source dataset
uspto-grants-2015_04
Patent number
US09012462B2

Reaction notes

Loading…