Isopropanol → N-{(1R,2R)-2-[5-chloro-2-(7-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide

HRID 1687004Notes

Reaction equation

HRID 1687004 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][S:16]([CH3:19])(=[O:18])=[O:17])[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[CH:24][C:25]2[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27][C:26]=2[CH:33]=1.C(O)(C)C>Cl.O1CCOCC1.O>[Cl:20][C:5]1[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]2[NH:15][S:16]([CH3:19])(=[O:18])=[O:17])=[N:7][C:2]([NH:21][C:22]2[CH:23]=[CH:24][C:25]3[CH2:31][CH2:30][C:29](=[O:32])[CH2:28][CH2:27][C:26]=3[CH:33]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 450982242-Amino-8,9-dihydro-5H-benzo[7]annulen-7(6H)-oneHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67263390N-{(1R,2R)-2-[5-chloro-2-(7-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamideYield 90%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

Into a microwave vial was placed N-[(1R,2R)-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide (50 mg, 0.0001 mol) and 2-amino-5,6,8,9-tetrahydro-benzocyclohepten-7-one (34 mg, 0.00019 mol) in isopropyl alcohol (5 mL, 0.06 mol) along with 3-4 drops of 4 M HCl in dioxane-water. The mixture was subjected microwaves at 130° C. for 10 minutes. The reaction mixture was resubjected to the same conditions for complete conversion of starting materials. The resulting solid was collected by filtration and washed with cold methylene chloride and dried in a vacuum oven at 50° C. overnight to give N-{(1R,2R)-2-[5-chloro-2-(7-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide as an off-white solid (43 mg, 60%). MP: 146-153° C.; 1HNMR (400 MHz, DMSO-d6) δ 9.34 (broad s, 1H), 7.98 (s, 1H), 7.65 (s, 1H), 7.44 (d, 1H, J=8.8 Hz), 7.18 (d, 1H, J=8 Hz), 7.14 (d, 1H, J=8 Hz), 6.99 (broad s, 1H), 3.85 (m, 1H), 3.57 (m, 1H), 2.94 (s, 3H), 2.84 (dd, 4H, J=7 Hz), 2.54 (m, 4H), 2.06 (m, 2H), 1.70 (d, 2H, J=11 Hz), 1.19-1.38 (m, 4H); MS (m/e) 478 (M+1).

Workup

  1. customat 130° C.
  2. customfor 10 minutes
  3. filtrationThe resulting solid was collected by filtration
  4. washwashed with cold methylene chloride
  5. customdried in a vacuum oven at 50° C. overnight

Sources & evidence

ORD record
ord-29664b6207ee4474ab5a44f644f255c9
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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