Ammonium Chloride → N-(5-bromo-3-methyl-2-pyridinyl)-9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 79119

Reaction equation

HRID 79119 reaction equation
CC([O-])(C)C.[Na+].[CH:7]1([N:12]2[C:16]3[N:17]=[C:18]([NH2:21])[N:19]=[CH:20][C:15]=3[C:14]3[CH:22]=[CH:23][N:24]=[CH:25][C:13]2=3)[CH2:11][CH2:10][CH2:9][CH2:8]1.Br[C:27]1[C:32]([CH3:33])=[CH:31][C:30]([Br:34])=[CH:29][N:28]=1.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.[NH4+].[Cl-]>O1CCOCC1.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]>[Br:34][C:30]1[CH:31]=[C:32]([CH3:33])[C:27]([NH:21][C:18]2[N:19]=[CH:20][C:15]3[C:14]4[CH:22]=[CH:23][N:24]=[CH:25][C:13]=4[N:12]([CH:7]4[CH2:8][CH2:9][CH2:10][CH2:11]4)[C:16]=3[N:17]=2)=[N:28][CH:29]=1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 8176802,5-Dibromo-3-methylpyridineHCID 23676156Sodium t-butoxideHCID 582995859-Cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 58299572N-(5-bromo-3-methyl-2-pyridinyl)-9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

Sodium 2-methylpropan-2-olate (0.142 g, 1.48 mmol) was combined with compound 4 (0.125 g, 0.493 mmol) and 2,5-dibromo-3-methylpyridine (0.149 g, 0.592 mmol) in 1,4-dioxane (3 ml). The reaction mixture was degassed by bubbling nitrogen through the solution for ˜1 mM, followed by the addition of XANTPHOS (0.0428 g, 0.0740 mmol) and Pd2(dba)3 (0.0339 g, 0.0370 mmol). The reaction was heated to 140° C. using microwave irradiation for 1 hour. The reaction mixture was poured into sat. NH4Cl and extracted with 10% isopropanol/DCM. The organic layer was dried with MgSO4 and concentrated in vacuum. Purification by flash column chromatography, eluting with a gradient of DCM-5% methanol/DCM provided compound 77 as a yellow solid (150 mg, 71%). LCMS-ESI (POS), M/Z, M+1: Found 423.1

Workup

  1. customThe reaction mixture was degassed
  2. customby bubbling nitrogen through the solution for ˜1 mM
  3. custommicrowave irradiation for 1 hour
  4. extractionextracted with 10% isopropanol/DCM
  5. dry with materialThe organic layer was dried with MgSO4
  6. concentrationconcentrated in vacuum
  7. customPurification by flash column chromatography
  8. washeluting with a gradient of DCM-5% methanol/DCM provided compound 77 as a yellow solid (150 mg, 71%)

Sources & evidence

ORD record
ord-c77b1ceb3c1845e0aa8b5f6dde4601fd
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Linked notes

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