1-Methyl-1H-indole-2-carbonyl chloride → N-[4-(4-amino-7-iodofuro[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide

HRID 17193Notes

Reaction equation

HRID 17193 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[C:13]([NH2:18])=[N:14][CH:15]=[C:16]([I:17])[C:11]=3[O:10][CH:9]=2)=[CH:4][C:3]=1[O:19][CH3:20].[CH3:21][N:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=[C:23]1[C:31](Cl)=[O:32]>N1C=CC=CC=1>[NH2:18][C:13]1[C:12]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:31]([C:23]4[N:22]([CH3:21])[C:30]5[C:25]([CH:24]=4)=[CH:26][CH:27]=[CH:28][CH:29]=5)=[O:32])=[C:3]([O:19][CH3:20])[CH:4]=3)=[CH:9][O:10][C:11]=2[C:16]([I:17])=[CH:15][N:14]=1

Participants

4

Reactant 2

HCID 123033141-Methyl-1H-indole-2-carbonyl chlorideHCID 184507093-(4-Amino-3-methoxyphenyl)-7-iodofuro[3,2-c]pyridin-4-amine

Product 1

HCID 18451296N-[4-(4-amino-7-iodofuro[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamideYield 89.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-(4-amino-3-methoxyphenyl)-7-iodofuro[3,2-c]pyridin-4-amine (2.53 g, 6.65 mmol) in pyridine (30 mL) was cooled to 0° C. and 1-methyl-1H-2-indolecarbonyl chloride (2.57 g, 13.3 mmol) was added. The mixture was stirred for 15 minutes at 0° C. and then allowed to rise to ambient temperature over an 18 hour time period. The solvent was removed in vacuo and the residue was dissolved in water (50 mL) and brought to pH 12 with 0.1 N aqueous sodium hydroxide, at which point a precipitate formed. The suspension was extracted with dichloromethane (4×25 mL) and the combined organic layers were washed with brine (25 mL) and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give the title compound (3.21 g, 89%) as a yellow solid. 1H NMR (DMSO-d6, 400 MHz) δ 9.48 (s, 1H), 8.14 (s, 1H), 8.08 (s, 1H), 8.04 (t, 1H), 7.71 (d, 1H), 7.59 (d, 1H), 7.30-7.37 (m, 2H), 7.25 (d, 1H), 7.11-7.18 (m, 2H), 5.75-5.83 (bs, 2H), 4.04 (s, 3H), 3.93 (s, 3H); RP-HPLC (Conditions d) Rt 8.73 min.; MS: MH+ 539.

Workup

  1. waitto rise to ambient temperature over an 18 hour
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in water (50 mL)
  4. customformed
  5. extractionThe suspension was extracted with dichloromethane (4×25 mL)
  6. washthe combined organic layers were washed with brine (25 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-51298a83792a46da994f8f518935dfaa
Source dataset
uspto-grants-2010_06
Patent number
US07737160B2

Reaction notes

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