Tert-Butylamine → N-(tert-butyl)-6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine

HRID 590787Notes

Reaction equation

HRID 590787 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[C:8](I)=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.[C:31]([NH2:35])([CH3:34])([CH3:33])[CH3:32].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.CC(C)([O-])C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[C:31]([NH:35][C:8]1[C:5]2[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][C:4]=2[N:10]([C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:9]=1)([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 6385Tert-ButylamineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 895258586-Chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 118272314N-(tert-butyl)-6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amineYield 24.5%

Reagents, catalysts & solvents 1

HCID 25112666BrettPhos PalladacycleCatalyst

Conditions

Temperature
110 °C

Procedure

A mixture of 6-chloro-3-iodo-1-trityl-1H-pyrazolo[4,3-c]pyridine (1000 mg, 1.917 mmol), tert-butylamine (565 μl, 5.75 mmol), brettphos palladacycle (77 mg, 0.096 mmol), 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl (44.7 mg, 0.096 mmol) and sodium tert-butoxide (553 mg, 5.75 mmol) were degassed. Toluene (9583 μl) was added to and reaction system was degassed and heated at 110° C. for 8 h. Solvent was evaporated in vacuo and partioned between water and EtOAc. Aqueous layer was extracted with EtOAc (2×) and combined organics were washed with water and saturated aqeous Brine, dried over Na2SO4 and concentrated in vacuo on silica. Material was purified by normal phase column chromotography eluting with EtOAc/Hex (0-15%) affording N-(tert-butyl)-6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-amine (219 mg, 0.469 mmol, 24.47% yield) as a white solid. 1H NMR (ppm, 500 MHz, DMSO-d6) δ 8.81 (s, 1H), 7.52-7.13 (m, 15H), 6.30 (s, 1H), 5.76 (s, 1H), 1.24 (s, 9H). MS ESI calc'd. For C29H27ClN4[M+H]+ 467. found 467.

Workup

  1. customwere degassed
  2. additionToluene (9583 μl) was added to and
  3. customreaction system
  4. customwas degassed
  5. customSolvent was evaporated in vacuo
  6. extractionAqueous layer was extracted with EtOAc (2×)
  7. washcombined organics were washed with water and saturated aqeous Brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo on silica
  10. customMaterial was purified by normal phase column chromotography
  11. washeluting with EtOAc/Hex (0-15%)

Sources & evidence

ORD record
ord-ec1db8a604b346e3b33cfdb104552311
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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