(S)-3-(7-amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,1,1-trifluoro-propan-2-ol → N-((1R,2R)-2-{5-Chloro-2-[3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide

HRID 1040829Notes

Reaction equation

HRID 1040829 reaction equation
[NH2:1][C:2]1[CH:19]=[CH:18][C:5]2[CH2:6][CH2:7][N:8]([CH2:11][C@H:12]([OH:17])[C:13]([F:16])([F:15])[F:14])[CH2:9][CH2:10][C:4]=2[CH:3]=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:1][C:2]2[CH:19]=[CH:18][C:5]3[CH2:6][CH2:7][N:8]([CH2:11][C@H:12]([OH:17])[C:13]([F:16])([F:14])[F:15])[CH2:9][CH2:10][C:4]=3[CH:3]=2)=[N:22][CH:23]=1

Participants

3

Reactant 2

HCID 67264395(S)-3-(7-amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,1,1-trifluoro-propan-2-olHCID 86633854N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Product 1

HCID 67264152N-((1R,2R)-2-{5-Chloro-2-[3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide

Procedure

N-((1R,2R)-2-{5-Chloro-2-[3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide was prepared from (S)-3-(7-amino-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,1,1-trifluoro-propan-2-ol and N-[(1R,2R)-2-(2,5-dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide in an analogous manner to Example 328. Product isolated as a pale yellow foam (88 mg, 44%). LCMS (m/e) 577 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.95 (s, 1H), 7.37-7.25 (m, 1H), 7.07 (d, 1H, J=8.0 Hz), 6.82 (s, 1H), 5.41 (d, 1H, J=7.8 Hz), 5.38-5.30 (m, 1H), 4.48-4.32 (m, 1H), 4.13-4.02 (m, 1H), 3.93-3.82 (m, 1H), 3.30-3.19 (m, 1H), 3.03-2.79 (m, 7H), 2.81 (s, 3H), 2.78-2.65 (m, 3H), 2.30-2.19 (m, 2H), 1.91-1.80 (m, 2H), 1.47-1.32 (m, 4H).

Sources & evidence

ORD record
ord-7e19de8893f942e3b6d2ed516c359660
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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