N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide → n-((1r,2r)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5h-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide

HRID 1687316Notes

Reaction equation

HRID 1687316 reaction equation
[F:1][CH:2]([F:19])[CH2:3][NH:4][CH:5]1[CH2:11][CH2:10][C:9]2[C:12](OC)=[C:13]([NH2:16])[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1.Cl[C:21]1[N:26]=[C:25]([NH:27][C@@H:28]2[CH2:33][CH2:32][CH2:31][CH2:30][C@H:29]2[NH:34][S:35]([CH3:38])(=[O:37])=[O:36])[C:24]([Cl:39])=[CH:23][N:22]=1>>[Cl:39][C:24]1[C:25]([NH:27][C@@H:28]2[CH2:33][CH2:32][CH2:31][CH2:30][C@H:29]2[NH:34][S:35]([CH3:38])(=[O:37])=[O:36])=[N:26][C:21]([NH:16][C:13]2[CH:14]=[CH:15][C:8]3[CH2:7][CH2:6][CH:5]([NH:4][CH2:3][CH:2]([F:19])[F:1])[CH2:11][CH2:10][C:9]=3[CH:12]=2)=[N:22][CH:23]=1

Participants

3

Reactant 2

HCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamideHCID 131729570N*7*-(2,2-Difluoro-ethyl)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocycloheptene-2,7-diamine

Product 1

HCID 87330241n-((1r,2r)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5h-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamideYield 60.7%

Procedure

In an analogous procedure to Example 651, part c, N*7*-(2,2-Difluoro-ethyl)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocycloheptene-2,7-diamine was combined with N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide to yield N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide (382.94 mg, 60.7% yield) as a white foam. 1H-NMR (CDCl3) δ 7.92 (m, 2H), 7.29 (m, 1H), 6.88 (d, J=8.17 Hz, 1H), 5.83 (m, 1H), 5.42 (m, 1H), 3.90 (m, 1H), 3.72 (s, 3H), 3.25 (m, 2H), 3.00 (t, J=15.0 Hz, 2H), 2.78 (m, 5H), 2.63 (m, 1H), 2.51 (m, 1H), 2.22 (m, 2H), 1.85 (m, 2H), 1.37 (m, 6H). LC/MS=573 (M+H).

Sources & evidence

ORD record
ord-ad2a0e695bb94315ad8037680b85db4b
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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