1,8-Diazabicyclo(5.4.0)undec-7-ene → 4-(2-Methyl-1H-indol-5-yloxy)-5,8-dihydro-6H-pyrido[3,4-d]pyrimidine-7-carboxylic acid tert-butyl ester

HRID 45070

Reaction equation

HRID 45070 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:14](=[O:18])[NH:13][CH:12]=[N:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1CCN2C(=NCCC2)CC1.[CH3:63][C:64]1[NH:65][C:66]2[C:71]([CH:72]=1)=[CH:70][C:69](O)=[CH:68][CH:67]=2>>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([O:18][C:69]3[CH:70]=[C:71]4[C:66](=[CH:67][CH:68]=3)[NH:65][C:64]([CH3:63])=[CH:72]4)=[N:13][CH:12]=[N:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 833362-methyl-1H-indol-5-olHCID 2724699PyBOPHCID 135741723tert-butyl 4-hydroxy-5H,6H,7H,8H-pyrido[3,4-d]pyrimidine-7-carboxylate

Product 1

HCID 593946124-(2-Methyl-1H-indol-5-yloxy)-5,8-dihydro-6H-pyrido[3,4-d]pyrimidine-7-carboxylic acid tert-butyl ester

Procedure

To a stirring solution of 4-oxo-4,5,6,8-tetrahydro-3H-pyrido[3,4-d]pyrimidine-7-carboxylic acid tert-butyl ester, Example 31-A, (300 mg, 1.2 mmol) in I (5 mL) is added PyBOP (800 mg, 1.55 mmol) and DBU (0.2 mL, 1.43 mmol). After 20 min 2-methyl-1H-indol-5-ol (211 mg, 1.43 mmol) is added. The mixture is then stirred at room temperature for 16 h. At that point the reaction is concentrated under reduced pressure and the residue is dissolved in EtOAc and washed by water and brine. The organic layer is dried over sodium sulfate, concentrated under reduced pressure. The residue is purified by FCC (EtOAc/heptane from 0% to 40%) to give the title compound. MS (ESI) m/z 381.0 (M+1).

Workup

  1. concentrationAt that point the reaction is concentrated under reduced pressure
  2. dissolutionthe residue is dissolved in EtOAc
  3. washwashed by water and brine
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by FCC (EtOAc/heptane from 0% to 40%)

Sources & evidence

ORD record
ord-be64b4387cef41bd830bd1334a6fb130
Source dataset
uspto-grants-2013_09
Patent number
US08541432B2

Linked notes

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