Water → US9777003, Example 228

HRID 628451Notes

Reaction equation

HRID 628451 reaction equation
[CH2:1]([N:8]1[C:12]2[CH:13]=[C:14](Cl)[C:15]3[N:16]([C:17]([CH3:20])=[N:18][N:19]=3)[C:11]=2[CH:10]=[C:9]1[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:23]1([CH2:26][NH2:27])[CH2:25][CH2:24]1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN1CCCC1=O.CC(C1C=C(C(C)C)C(C2C(P(C(C)(C)C)C(C)(C)C)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.CS([O-])(=O)=O.C1C=[C-]C(C2C(N)=CC=CC=2)=CC=1.[Pd+2]>[CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([NH:27][CH2:26][CH:23]3[CH2:25][CH2:24]3)[C:15]3[N:16]([C:17]([CH3:20])=[N:18][N:19]=3)[C:11]=2[CH:10]=[C:9]1[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 75646CyclopropanemethanamineHCID 1181596216-benzyl-4-chloro-1,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 118159597US9777003, Example 228

Reagents, catalysts & solvents 2

HCID 86346478Ditert-butyl-[3,6-dimethoxy-2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane;methanesulfonate;palladium(2+);2-phenylanilineCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 6-benzyl-4-chloro-1,7-dimethyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine (20.0 mg, 0.0644 mmol, from Step 7), cyclopropylmethylamine (51 μL, 0.60 mmol, Aldrich), tBuBrettPhos Pd G3 (6.5 mg, 0.0076 mmol, Aldrich) and Cs2CO3 (0.045 g, 0.14 mmol) in N-methylpyrrolidinone (0.3 mL) and water (0.030 g) was degassed and heated at 100° C. for 4.5 h, after which time the reaction mixture was filtered and the product was purified by preparative HPLC-MS (Waters XBridge C18, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH). Yield: (10.5 mg, 47%).

Workup

  1. customwas degassed
  2. filtrationafter which time the reaction mixture was filtered
  3. customthe product was purified by preparative HPLC-MS (Waters XBridge C18
  4. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-03595e32b47143d6b92f0abc266b72d9
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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