Tricyclohexylphosphine → HCID 86719395, compound

HRID 510348Notes

Reaction equation

HRID 510348 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[N:23]([CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])[N:22]=[N:21][CH:20]=4)=[CH:13][CH:12]=3)=[C:9](Br)[N:8]([C@@H:33]3[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:45]B(O)O.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[N:23]([CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])[N:22]=[N:21][CH:20]=4)=[CH:13][CH:12]=3)=[C:9]([CH3:45])[N:8]([C@@H:33]3[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 75806TricyclohexylphosphineHCID 139377Methylboronic AcidHCID 86719393HCID 86719393, compound

Product 1

HCID 86719395HCID 86719395, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (R)-tert-butyl 3-(4-amino-6-bromo-5-(4-((1-(pivaloyloxymethyl)-1H-1,2,3-triazol-5-yl)methoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (82) (344 mg, 0.51 mmol) in toluene (10 mL) were added methylboronic acid (306 mg, 5.1 mmol), Pd2(dba)3 (23.3 mg, 0.0255 mmol), PCy3 (14.3 mg, 0.051 mmol) and K3PO4.3H2O (407 mg, 1.53 mmol). The resulting mixture was purged with N2 for three times before heated to 120° C. overnight. The solvents were removed under vacuum and the residue was purified by flash chromatography (silica gel, 0 to 15% MeOH in DCM, with 0.5% TEA) to provide (R)-tert-butyl 3-(4-amino-6-methyl-5-(4-((1-(pivaloyloxymethyl)-1H-1,2,3-triazol-5-yl)methoxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (83) (188 mg, 61%). LC-MS (ESI): m/z (M+1) 605.0.

Workup

  1. customThe resulting mixture was purged with N2 for three times
  2. customThe solvents were removed under vacuum
  3. customthe residue was purified by flash chromatography (silica gel, 0 to 15% MeOH in DCM, with 0.5% TEA)

Sources & evidence

ORD record
ord-8e6983b799ec4052b2e952e145506d0a
Source dataset
uspto-grants-2015_08
Patent number
US09096604B2

Reaction notes

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