1,4-Dioxane hydrochloride → HCID 25158499, compound

HRID 1041598Notes

Reaction equation

HRID 1041598 reaction equation
[NH2:1][C:2]1[C:12]2[CH2:11][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:9][C:8](=[O:20])[NH:7][C:6]=2[CH:5]=[CH:4][C:3]=1[O:21][CH3:22].Cl[C:24]1[N:29]=[C:28]([NH:30][C@@H:31]2[CH2:36][CH2:35][CH2:34][CH2:33][C@H:32]2[NH:37][S:38]([CH3:41])(=[O:40])=[O:39])[C:27]([Cl:42])=[CH:26][N:25]=1.Cl.O1CCOCC1>COCCO>[CH2:13]([N:10]1[CH2:11][C:12]2[C:2]([NH:1][C:24]3[N:29]=[C:28]([NH:30][C@@H:31]4[CH2:36][CH2:35][CH2:34][CH2:33][C@H:32]4[NH:37][S:38]([CH3:41])(=[O:39])=[O:40])[C:27]([Cl:42])=[CH:26][N:25]=3)=[C:3]([O:21][CH3:22])[CH:4]=[CH:5][C:6]=2[NH:7][C:8](=[O:20])[CH2:9]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 204431481,4-Dioxane hydrochlorideHCID 67264415HCID 67264415, compoundHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 25158499HCID 25158499, compound

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 6-amino-4-benzyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (75 mg, 0.25 mmol) and N-[(1R,2R)-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (85 mg, 0.25 mmol) in 2-methoxyethanol (2 mL) was added 4N HCl-dioxane (0.20 mL). The mixture was heated to 90° C. for two hours whereupon LCMS showed complete consumption of the aniline. After being cooled to room temperature, triethylamine was added to pH 9 and the crude product was purified by preparative tlc (7% MeOH-DCM) to afford N-{(1R,2R)-2-[2-(4-benzyl-7-methoxy-2-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-6-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as a light brown foam; 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.02 (s, 2H), 7.35 (m, 5H), 7.10 (d, J=8 Hz, 1H), 7.03 (d, J=8 Hz, 1H), 6.78 (m, 1H), 4.65 (m, 1H), 4.30 (m, 1H), 3.70 (s, 3H), 3.65 (s, 2H), 3.60 (s, 2H), 3.26 (s, 2H), 2.89 (s, 3H), 1.97 (m, 2H), 1.68 (m, 2H), 1.38 (m, 2H), 1.25 (m, 2H); MS (m/e) 601 (M+1).

Workup

  1. customconsumption of the aniline
  2. temperatureAfter being cooled to room temperature
  3. additiontriethylamine was added to pH 9
  4. customthe crude product was purified by preparative tlc (7% MeOH-DCM)

Sources & evidence

ORD record
ord-a5043e44e3fe44bda9256c581122a7d0
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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