Trifluoroacetic acid → 5-Chloro-N*4*-(2-ethyl-4-morpholin-4-yl-phenyl)-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine

HRID 1040983Notes

Reaction equation

HRID 1040983 reaction equation
[F:1][C:2]([F:18])([F:17])[CH2:3][NH:4][CH:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[C:13]([NH2:16])[CH:14]=[CH:15][C:8]=2[CH2:7][CH2:6]1.[CH3:19][C:20]1(C)[C@]2(CS(O)(=O)=O)C(C[C@H]1CC2)=O.Cl[C:35]1[N:40]=[C:39]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)=[CH:44][C:43]=2OC)[C:38]([Cl:56])=[CH:37][N:36]=1.C(O)(C(F)(F)F)=O>>[Cl:56][C:38]1[C:39]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)=[CH:44][C:43]=2[CH2:19][CH3:20])=[N:40][C:35]([NH:16][C:13]2[CH:14]=[CH:15][C:8]3[CH2:7][CH2:6][CH:5]([NH:4][CH2:3][C:2]([F:17])([F:18])[F:1])[CH2:11][CH2:10][C:9]=3[CH:12]=2)=[N:36][CH:37]=1

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 65617D-Camphorsulfonic AcidHCID 86633851(2,5-Dichloropyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amineHCID 131729561N*7*-(2,2,2-trifluoro-ethyl)-6,7,8,9-tetrahydro-5H-benzocycloheptene-2,7-diamine

Product 1

HCID 1317295625-Chloro-N*4*-(2-ethyl-4-morpholin-4-yl-phenyl)-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamineYield 8.4%

Procedure

In an analogous procedure to Example 651, part c, N*7*-(2,2,2-Trifluoro-ethyl)-6,7,8,9-tetrahydro-5H-benzocycloheptene-2,7-diamine (75 mg, 0.290 mmol) was combined with DL-10-camphorsulfonic acid (101 mg, 0.436 mmol) and (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine (103 mg, 0.290 mmol) to prepare 5-Chloro-N*4*-(2-ethyl-4-morpholin-4-yl-phenyl)-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine (13.82 mg, 8.4% yield) as a yellow TFA salt. 1H-NMR (CDCl3) δ 8.24 (dd, J=26.9, 8.81 Hz, 1H), 8.00 (m, 1H), 7.87 (br s, 1H), 7.47 (m, 1H), 6.95 (m, 1H), 6.53 (m, 3H), 3.89 (m, 7H), 3.16 (m, 4H), 2.84 (m, 2H), 2.69 (m, 2H), 2.04 (m, 2H), 1.29 (m, 2H). LC/MS (ESI+)=571 (M+H). MP=155° C.

Sources & evidence

ORD record
ord-f38cd162a4b8422c96b4551bde30af64
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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