Potassium Phosphate, Tribasic → 7-(2-Aminopyrimidin-5-yl)-1-[(dicyclopropylmethyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide

HRID 1970999Notes

Reaction equation

HRID 1970999 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:14]([NH:15][CH:16]([CH:20]4[CH2:22][CH2:21]4)[CH:17]4[CH2:19][CH2:18]4)=[N:13][CH:12]=[C:11]([C:23]([NH2:25])=[O:24])[C:7]=3[NH:8][C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[N:36][C:37]([NH2:40])=[N:38][CH:39]=2)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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]>[NH2:40][C:37]1[N:38]=[CH:39][C:34]([C:2]2[CH:3]=[CH:4][C:5]3[C:6]4[C:14]([NH:15][CH:16]([CH:17]5[CH2:19][CH2:18]5)[CH:20]5[CH2:22][CH2:21]5)=[N:13][CH:12]=[C:11]([C:23]([NH2:25])=[O:24])[C:7]=4[NH:8][C:9]=3[CH:10]=2)=[CH:35][N:36]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 177502122-Aminopyrimidine-5-boronic acid, pinacol esterHCID 565953257-Chloro-1-[(dicyclopropylmethyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide

Product 1

HCID 426359017-(2-Aminopyrimidin-5-yl)-1-[(dicyclopropylmethyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 7-chloro-1-[(dicyclopropylmethyl)amino]-5H-pyrido[4,3-b]indole-4-carboxamide (7.1 g, 20.0 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrimidin-2-ylamine (6.2 g, 28 mmol), Pd2(dba)3 (1.83 g, 2.0 mmol), tricyclohexylphosphine (1.4 g, 5.0 mmol), and K3PO4 (1.27 M in water, 53.8 mL, 68.3 mmol) in dioxane (400 mL) was purged with nitrogen for 20 min, heated to 100° C. for 4 h, cooled to room temperature, and concentrated. The residue was diluted with 50% brine, and extracted with EtOAc (×3). The combined organics were washed with brine, dried (sodium sulfate) and purified by flash chromatography to give the title compound as a white solid. 1H NMR (500 MHz, CD3SOCD3) δ 11.50 (s, 1H); 8.61 (s, 2H); 8.45 (s, 1H); 8.43 (d, 1H); 7.92 (s, 1H); 7.83 (br s, 1H); 7.49 (dd, 1H); 7.18 (br s, 1H); 6.78 (s, 2H); 6.51 (d, 1H); 3.63 (q, 1H); 1.38 (m, 2H); 0.51 (m, 2H); 0.36 (m, 6H). LRMS (APCI) calc'd for (C23H23N7O) [M+H]+, 414.2. found 414.1.

Workup

  1. customwas purged with nitrogen for 20 min
  2. temperaturecooled to room temperature
  3. concentrationconcentrated
  4. additionThe residue was diluted with 50% brine
  5. extractionextracted with EtOAc (×3)
  6. washThe combined organics were washed with brine
  7. dry with materialdried (sodium sulfate)
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-fd9345c93c9d4066982cb7c2c3e56661
Source dataset
uspto-grants-2013_04
Patent number
US08431569B2

Reaction notes

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