Ammonium Chloride → 1,1-dimethylethyl 4-(6-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-5-methyl-3-pyridinyl)-1-piperazinecarboxylate

HRID 79120Notes

Reaction equation

HRID 79120 reaction equation
CC([O-])(C)C.[Na+].Br[C:8]1[CH:9]=[C:10]([CH3:33])[C:11]([NH:14][C:15]2[N:16]=[CH:17][C:18]3[C:23]4[CH:24]=[CH:25][N:26]=[CH:27][C:22]=4[N:21]([CH:28]4[CH2:32][CH2:31][CH2:30][CH2:29]4)[C:19]=3[N:20]=2)=[N:12][CH:13]=1.[N:34]1([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]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]>[CH:28]1([N:21]2[C:19]3[N:20]=[C:15]([NH:14][C:11]4[N:12]=[CH:13][C:8]([N:37]5[CH2:36][CH2:35][N:34]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39][CH2:38]5)=[CH:9][C:10]=4[CH3:33])[N:16]=[CH:17][C:18]=3[C:23]3[CH:24]=[CH:25][N:26]=[CH:27][C:22]2=3)[CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 58299572N-(5-bromo-3-methyl-2-pyridinyl)-9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 582996341,1-dimethylethyl 4-(6-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-5-methyl-3-pyridinyl)-1-piperazinecarboxylateYield 53.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
140 °C

Procedure

Sodium 2-methylpropan-2-olate (0.100 g, 1.06 mmol) was combined with compound 77 (0.150 g, 0.354 mmol) and tert-butyl 1-piperazinecarboxylate (0.099 g, 0.532 mmol) in 1,4-dioxane (3 ml). Nitrogen was bubbled through the solution for 1 min before adding XANTPHOS (0.031 g, 0.053 mmol) and Pd2(dba)3 (0.024 g, 0.026 mmol). The reaction mixture 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 over MgSO4 and concentrated in vacuum. The crude product was purified by flash column chromatography, eluting with a gradient of DCM-7% methanol/DCM to provide compound 78 as a brown oil (100 mg). LCMS-ESI (POS), M/Z, M+1: Found 529.3.

Workup

  1. customNitrogen was bubbled through the solution for 1 min
  2. custommicrowave irradiation for 1 hour
  3. extractionextracted with 10% isopropanol/DCM
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuum
  6. customThe crude product was purified by flash column chromatography
  7. washeluting with a gradient of DCM-7% methanol/DCM

Sources & evidence

ORD record
ord-9b24c651f4784643ae175da9ab8670a6
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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