Water → N1-(2-dimethylaminoethyl)-N4-[4-(1H-indol-3-yl)pyrimidin-2-yl]-5-methoxy-N1-methylbenzene-1,2,4-triamine

HRID 1842820Notes

Reaction equation

HRID 1842820 reaction equation
O.[CH3:2][N:3]([CH3:35])[CH2:4][CH2:5][N:6]([CH3:34])[C:7]1[C:12]([N+:13]([O-])=O)=[CH:11][C:10]([NH:16][C:17]2[N:22]=[C:21]([C:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[NH:25][CH:24]=3)[CH:20]=[CH:19][N:18]=2)=[C:9]([O:32][CH3:33])[CH:8]=1.[NH4+].[Cl-]>[Fe].C(O)C>[CH3:35][N:3]([CH3:2])[CH2:4][CH2:5][N:6]([CH3:34])[C:7]1[C:12]([NH2:13])=[CH:11][C:10]([NH:16][C:17]2[N:22]=[C:21]([C:23]3[C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[NH:25][CH:24]=3)[CH:20]=[CH:19][N:18]=2)=[C:9]([O:32][CH3:33])[CH:8]=1

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 71240878N1-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine2×

Product 1

HCID 86677322N1-(2-dimethylaminoethyl)-N4-[4-(1H-indol-3-yl)pyrimidin-2-yl]-5-methoxy-N1-methylbenzene-1,2,4-triamineYield 97%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
105 °C

Procedure

Water (4 mL) was added in one portion to a mixture of N′-(2-dimethylaminoethyl)-N-[4-(1H-indol-3-yl)pyrimidin-2-yl]-2-methoxy-N′-methyl-5-nitrobenzene-1,4-diamine (Intermediate 169, 270 mg, 0.59 mmol), iron (196 mg, 3.51 mmol), NH4Cl (21.9 mg, 0.41 mmol) and ethanol (24 mL). The resulting mixture was heated at 105° C. for 3 h then filtered through diatomaceous earth (Celite™). The filtrate was concentrated in vacuo and then part-purified by ion exchange chromatography, using an SCX column and eluting with 0.35M methanolic ammonia. Appropriate fractions were combined and concentrated in vacuo to give the title compound (244 mg, 97%) as a brown solid which was used without further purification; 1H NMR: 2.18 (6H, s), 2.37 (2H, s), 2.64 (3H, s), 2.90 (2H, s), 3.76 (3H, s), 6.77 (1H, s), 7.03-7.26 (3H, m), 7.46 (1H, d), 7.52 (1H, s), 7.74 (1H, s), 8.18-8.35 (2H, m), 8.42 (1H, d), 11.72 (1H, s); m/z: ES+ MH+ 432.

Workup

  1. filtrationthen filtered through diatomaceous earth (Celite™)
  2. concentrationThe filtrate was concentrated in vacuo
  3. custompart-purified by ion exchange chromatography
  4. washeluting with 0.35M methanolic ammonia
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f952effef33245baad8aac300087ba72
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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