Ammonia → HCID 67263327, compound

HRID 1040918Notes

Reaction equation

HRID 1040918 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][NH:10][CH2:9][CH2:8][N:7]([CH3:12])[C:6]=2[CH:13]=1.COC(O)C.Cl[C:20]1[N:25]=[C:24]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]2[NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[C:23]([Cl:38])=[CH:22][N:21]=1.Cl.O1CCOCC1.N>CO.ClCCl>[Cl:38][C:23]1[C:24]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@H:28]2[NH:33][S:34]([CH3:37])(=[O:36])=[O:35])=[N:25][C:20]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[CH2:11][NH:10][CH2:9][CH2:8][N:7]([CH3:12])[C:6]=3[CH:13]=2)=[N:21][CH:22]=1

Participants

9

Reactant 6

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 30156371-MethoxyethanolHCID 57853856HCID 57853856, compoundHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67263327HCID 67263327, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To 40 ml sure-seal reaction vial, 8-Amino-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepine (0.33 g, 2 mmoles), methoxy ethanol (6 ml), and N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (0.51 g, 1.1.5 mmole), 4M HCl in dioxane (1 ml, 4 mmoles) were added. The reaction was heated to reflux for 3 hours. Upon cooling to room temperature, the solvent was then removed under vacuum to afford a yellow solid. The product (0.53 g, 74% yield) was isolated via column chromatography with dichloromethane and ammonia in methanol (2% to 30% ammonia in methanol) as eluant. NMR 1H-(DMSO)-δ-9.02 (bs, 1H), 7.93 (s, 1H), 7.32 (d, 1H, J=8.59 Hz), 7.16 (bs, 2H), 6.93 (d, 1H, J=7.58), 6.67 (d, 1 h, J=7.58 Hz), 3.80-3.90 (bm, 1H), 3.64 (s, 2H), 3.30-3.40 (bm, 1H), 3.17 (d, 1H, 5.2 Hz), 2.92 (s, 3H), 2.83-2.90 (m, 4H), 2.82 (s, 3H), 1.95-2.12 (m, 2H), 1.65-1.75 (m, 2H), 1.15-1.48 (m, 4H). LCMS (ESI+) 480.13 (M+H); MP=153-206° C.

Workup

  1. customTo 40 ml sure-seal
  2. customreaction vial
  3. temperatureThe reaction was heated
  4. temperatureto reflux for 3 hours
  5. customthe solvent was then removed under vacuum
  6. customto afford a yellow solid

Sources & evidence

ORD record
ord-96c26a410669439b90977d17e7ad4113
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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