4-Methoxybenzylamine → N4-(1-(3-fluorobenzyl)-1H-indazol-5-yl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine

HRID 511789Notes

Reaction equation

HRID 511789 reaction equation
F[C:2]1[N:29]=[CH:28][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[N:16]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)[N:15]=[CH:14]4)[C:4]=2[CH:3]=1.[CH3:30][O:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][NH2:37])=[CH:34][CH:33]=1>CS(C)=O>[F:27][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=1)[CH2:20][N:16]1[C:17]2[C:13](=[CH:12][C:11]([NH:10][C:9]3[C:4]4[CH:3]=[C:2]([NH:37][CH2:36][C:35]5[CH:38]=[CH:39][C:32]([O:31][CH3:30])=[CH:33][CH:34]=5)[N:29]=[CH:28][C:5]=4[N:6]=[CH:7][N:8]=3)=[CH:19][CH:18]=2)[CH:14]=[N:15]1

Participants

4

Reactant 2

HCID 754524-MethoxybenzylamineHCID 681586436-fluoro-N-(1-(3-fluorobenzyl)-1H-indazol-5-yl)pyrido[3,4-d]-pyrimidin-4-amine

Product 1

HCID 86668929N4-(1-(3-fluorobenzyl)-1H-indazol-5-yl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamineYield 61%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
69 °C

Procedure

A mixture of compound 202 (3.00 g, 7.73 mmol) and 4-methoxybenzylamine (10.2 mL, 77.3 mmol) in dry DMSO (18 mL) was stirred under a nitrogen atmosphere at 68-70° C. (bath temperature) for 165 h. The solution was then cooled and petroleum ether (200 mL) was added. It was stirred at room temperature for 15 min. The layers were allowed to separate and the petroleum ether layer was decanted. This procedure was repeated with more petroleum ether (200 ml). Water (200 mL) was added and the mixture was stirred at room temperature for 45 min. The oil was deposited. Thus, the product was extracted into ethyl acetate; dried (MgSO4) and solvent removed to give a brown oil. It was purified by a silica column (EtOAc/petroleum ether: gradient from 30% to pure EtOAc) to give pure N4-(1-(3-fluorobenzyl)-1H-indazol-5-yl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (211) (2.38 g, 61%) as a yellow/orange solid, mp 196-198° C.; 1H NMR δ [(CD3)2SO] 9.75 (s, 1H), 8.72 (s, 1H), 8.29 (s, 1H), 8.22 (poorly resolved d, J=1.3 Hz, 1H), 8.15 (d, J=0.7 Hz, 1H), 7.73 (br d, J=9.0 Hz, 1H), 7.68 (dd, J=9.0, 1.8 Hz, 1H), 7.40-7.31 (m, 3H), 7.24-7.17 (m, 2H), 7.13-7.01 (m, 3H), 6.92-6.84 (m, 2H), 5.70 (s, 2H) 4.49 (d, J=6.3 Hz, 2H), 3.71 (s, 3H). Anal. Calcd for C29H24FN7O.1.5H2O: C, 65.40; H, 5.11; N, 18.41%. Found C, 65.45; H, 5.07; N, 18.58%.

Workup

  1. temperatureThe solution was then cooled
  2. stirringIt was stirred at room temperature for 15 min
  3. customto separate
  4. customthe petroleum ether layer was decanted
  5. additionWater (200 mL) was added
  6. stirringthe mixture was stirred at room temperature for 45 min
  7. extractionThus, the product was extracted into ethyl acetate
  8. dry with materialdried (MgSO4) and solvent
  9. customremoved
  10. customto give a brown oil
  11. customIt was purified by a silica column (EtOAc/petroleum ether: gradient from 30% to pure EtOAc)

Sources & evidence

ORD record
ord-7c755f3b6a604338a76a5c2f299a5b94
Source dataset
uspto-grants-2015_08
Patent number
US09101632B2

Reaction notes

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