4-Chloro-2-methylpyridine → HCID 68294290, compound

HRID 2279498Notes

Reaction equation

HRID 2279498 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:6]=2[N:7]=1.Cl[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=1.O(C(C)(C)C)[Na]>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].C1(C)C=CC=CC=1>[CH3:26][C:22]1[CH:21]=[C:20]([NH:1][C:2]2[N:3]=[CH:4][C:5]3[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:6]=3[N:7]=2)[CH:25]=[CH:24][N:23]=1

Participants

6

Reactant 3

HCID 5813924-Chloro-2-methylpyridineHCID 754876172-AMino-5,8-dihydro-6H-pyrido[3,4-d]pyriMidine-7-carboxylic acid tert-butyl esterHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 68294290HCID 68294290, compoundYield 33.2%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A tube was charged with 187 (300 mg, 1.20 mmol), Pd(dba)2 (34.5 mg, 0.0599 mmol), Binap-rac (74.6 mg, 0.120 mmol), 4-chloro-2-methylpyridine (229 mg, 1.80 mmol), and NaO-tert-Bu (230 mg, 2.40 mmol) and toluene (3 mL), sealed, degassed with nitrogen for 5 min then heated to 90° C. for 4 h. The reaction was cooled and filtered through a plug of CELITE®. The filtrate was concentrated and purified by reverse phase column chromatography (SP4) eluting with a MeCN/H2O gradient (5 to 85% MeCN) to afford 136 mg (33.2%) of tert-butyl 2-(2-methylpyridin-4-ylamino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (188).

Workup

  1. customsealed
  2. customdegassed with nitrogen for 5 min
  3. temperatureThe reaction was cooled
  4. filtrationfiltered through a plug of CELITE®
  5. concentrationThe filtrate was concentrated
  6. custompurified by reverse phase column chromatography (SP4)
  7. washeluting with a MeCN/H2O gradient (5 to 85% MeCN)

Sources & evidence

ORD record
ord-3ed0b03ef398414faa9e8f2f6eb5b51a
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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