تفاعل #166299

ord-a2ff19afe194443399156c5428e7ed28

معادلة التفاعل

Nc1ncc2c3ccncc3n(C3CCCC3)c2n1
Compound 4
Nc1ncc2c3ccncc3n(C3CCCC3)c2n1
9-Cyclopentyl-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-amine
CC(C)(C)OC(=O)N1CCN(C(=O)c2csc(Br)n2)CC1
compound 72
CC(C)(C)OC(=O)N1CCN(C(=O)c2csc(Br)n2)CC1
1,1-dimethylethyl 4-((2-bromo-1,3-thiazol-4-yl)carbonyl)-1-piperazinecarboxylate
CC(C)(C)OC(=O)N1CCN(C(=O)c2csc(Br)n2)CC1
compound 72
CC(C)(C)OC(=O)N1CCN(C(=O)c2csc(Br)n2)CC1
1,1-dimethylethyl 4-((2-bromo-1,3-thiazol-4-yl)carbonyl)-1-piperazinecarboxylate
CC(C)c1cc(C(C)C)c(-c2ccccc2P(C(C)(C)C)C(C)(C)C)c(C(C)C)c1
t-Butyl-XPhos
CC(C)(C)[O-].[Na+]
sodium 2-methylpropan-2-olate
CC(C)(C)[O-].[Na+]
sodium 2-methylpropan-2-olate
CC(C)c1cc(C(C)C)c(-c2ccccc2P(C(C)(C)C)C(C)(C)C)c(C(C)C)c1
t-Butyl-XPhos
CC(C)(C)OC(=O)N1CCN(C(=O)c2csc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)n2)CC1
compound 74
المردود 57.7%
CC(C)(C)OC(=O)N1CCN(C(=O)c2csc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)n2)CC1
1,1-dimethylethyl 4-((2-((9-cyclopentyl-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-1,3-thiazol-4-yl)carbonyl)-1-piperazinecarboxylate
المردود 57.7%

ظروف التفاعل

درجة الحرارة
60°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىThis mixture was degassed
  2. 2
    أخرىby bubbling nitrogen through this solution for ˜2 min
  3. 3
    درجة الحرارةwas heated overnight at 100° C
  4. 4
    درجة الحرارةThe reaction was cooled to 20° C.
  5. 5
    أخرىThe layers were partitioned
  6. 6
    غسيلthe aqueous layer was washed with ethyl acetate
  7. 7
    تجفيفThe combined organic fractions were dried over MgSO4
  8. 8
    تركيزconcentrated
  9. 9
    أخرىThe product was purified by flash column chromatography
  10. 10
    غسيلeluting with a gradient of DCM-6% methanol/0.3% NH4OH/DCM

الإجراء التجريبي

Compound 4 (0.075 g, 0.30 mmol) was combined with sodium 2-methylpropan-2-olate (0.085 g, 0.89 mmol) and compound 72 (0.14 g, 0.38 mmol) in toluene (2 mL). This mixture was degassed by bubbling nitrogen through this solution for ˜2 min followed by the addition of Pd2(dba)3 (0.014 g, 0.015 mmol) and t-Butyl-XPhos (0.025 g, 0.059 mmol). The reaction was heated overnight at 60° C. Additional compound 72, 0.28 g, 0.76 mmol), Pd2(dba)3 (25 mg), t-Butyl-XPhos (54 mg), and the sodium 2-methylpropan-2-olate (0.085 g, 0.89 mmol) were added to the reaction which was heated overnight at 100° C. The reaction was cooled to 20° C. and poured into a separation funnel, with ethyl acetate and water. The layers were partitioned and the aqueous layer was washed with ethyl acetate. The combined organic fractions were dried over MgSO4 and concentrated. The product was purified by flash column chromatography, eluting with a gradient of DCM-6% methanol/0.3% NH4OH/DCM to yield compound 74 (95 mg) as a brown film. LCMS-ESI (POS), M/Z, M+1: Found 549.3.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08841312B2uspto-grants-2014_09