1,4-Dioxane hydrochloride → HCID 67264357, compound

HRID 1041596Notes

Reaction equation

HRID 1041596 reaction equation
[NH2:1][C:2]1[C:3]([O:21][CH3:22])=[CH:4][C:5]2[CH2:11][N:10]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:9][C:8](=[O:19])[NH:7][C:6]=2[CH:20]=1.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>[CH2:12]([N:10]1[CH2:11][C:5]2[CH:4]=[C:3]([O:21][CH3:22])[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)=[CH:20][C:6]=2[NH:7][C:8](=[O:19])[CH2:9]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 204431481,4-Dioxane hydrochlorideHCID 67263433HCID 67263433, compoundHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67264357HCID 67264357, compound

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

To a solution of 8-amino-4-benzyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (55 mg, 0.19 mmol) and N-[(1R,2R)-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (63 mg, 0.19 mmol) in 2-methoxyethanol (2 mL) was added 4N HCl-dioxane (0.20 mL). The mixture was heated to reflux 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 (5% 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-8-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as a mustard yellow solid; 1H NMR (400 MHz, DMSO-d6) δ 9.68 (s, 1H), 7.96 (s, 2H), 7.73 (s, 1H), 7.35 (m, 5H), 7.05 (d, J=7 Hz, 1H), 6.93 (s, 1H), 6.85 (d, J=8.5 Hz, 1H), 4.55 (m, 1H), 3.86 (s, 3H), 3.70 (s, 2H), 3.64 (s, 2H), 3.06 (s, 2H), 2.88 (s, 3H), 1.97 (m, 2H), 1.63 (m, 2H), 1.38 (m, 2H), 1.23 (m, 2H); MS (m/e) 601 (M+1); mp 214° C. (dec.).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for two hours whereupon LCMS
  3. customconsumption of the aniline
  4. additiontriethylamine was added to pH 9
  5. customthe crude product was purified by preparative tlc (5% MeOH-DCM)

Sources & evidence

ORD record
ord-599b28a66f0d48998892777e1d3a88e5
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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