Dimethylformamide → 8-(2,5-Dichloro-pyrimidin-4-ylamino)-1,4-diethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one

HRID 1041037Notes

Reaction equation

HRID 1041037 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[CH:13][C:14]2[C:20](=[O:21])[N:19]([CH2:22][CH3:23])[CH2:18][CH2:17][N:16]([CH2:24][CH3:25])[C:15]=2[CH:26]=1.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+]>>[Cl:1][C:2]1[N:7]=[C:6]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[C:20](=[O:21])[N:19]([CH2:22][CH3:23])[CH2:18][CH2:17][N:16]([CH2:24][CH3:25])[C:15]=3[CH:26]=2)[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 2372592,4,5-TrichloropyrimidineHCID 672633818-Amino-1,4-diethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one

Product 1

HCID 866339098-(2,5-Dichloro-pyrimidin-4-ylamino)-1,4-diethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-oneYield 54.1%

Conditions

Temperature
80 °C

Procedure

To a mixture of 2,4,5-Trichloro-pyrimidine (0.315 g, 0.00172 mol), 8-Amino-1,4-diethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one (0.40 g, 0.0017 mol) in anhydrous N,N-Dimethylformamide (10 mL, 0.1 mol) was added Potassium carbonate (0.35 g, 0.0025 mol) and heated at 80° C. for 17 hours. The reaction was evaporated, water added and tan solid collected. This was chromatographed on a SiO2 prep plates with hexane/acetonitrile (1-1) giving 8-(2,5-Dichloro-pyrimidin-4-ylamino)-1,4-diethyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one as a cream colored solid (0.35 g, 54%); Mp 71-74° C.; LCMS (m/e) 380 (M); 1H-NMR (DMSO, 400 MHz) 9.50 (s, 1H), 8.42 (s, 1H), 7.45-7.43 (d, 1H, J=7.83 Hz), 7.35 (s, 1H), 7.21-7.19 (d, 1H, J=8.34 Hz), 3.54-3.48 (q, 2H, J=7.08 Hz), 3.43-3.41 (t, 2H, J=5.31 Hz), 3.32-3.28 (t, 2H, J=4.04 Hz), 3.21-3.16 (q, 2H, J=6.32 Hz), 1.16-1.11 (t, 3H, J=7.07 Hz), 1.20-1.18 (t, 3H, J=6.82 Hz).

Workup

  1. customThe reaction was evaporated
  2. additionwater added
  3. customtan solid collected
  4. customThis was chromatographed on a SiO2 prep plates with hexane/acetonitrile (1-1)

Sources & evidence

ORD record
ord-29a8acc5e4404eb0bf68859ac8929a49
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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