D-Camphorsulfonic Acid → 2-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5h-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-n-methyl-benzamide

HRID 1040982ノート

反応式

HRID 1040982 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([Cl:19])=[CH:4][N:3]=1.[F:20][C:21]([F:37])([F:36])[CH2:22][NH:23][CH:24]1[CH2:30][CH2:29][C:28]2[CH:31]=[C:32]([NH2:35])[CH:33]=[CH:34][C:27]=2[CH2:26][CH2:25]1.CC1(C)[C@]2(CS(O)(=O)=O)C(C[C@H]1CC2)=O.C(=O)(O)[O-].[Na+]>CC(O)C.C(Cl)Cl.O>[Cl:19][C:5]1[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])=[N:7][C:2]([NH:35][C:32]2[CH:33]=[CH:34][C:27]3[CH2:26][CH2:25][CH:24]([NH:23][CH2:22][C:21]([F:20])([F:36])[F:37])[CH2:30][CH2:29][C:28]=3[CH:31]=2)=[N:3][CH:4]=1

参加物

8

反応物 4

HCID 65617D-Camphorsulfonic AcidHCID 516892Sodium BicarbonateHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamideHCID 131729561N*7*-(2,2,2-trifluoro-ethyl)-6,7,8,9-tetrahydro-5H-benzocycloheptene-2,7-diamine

生成物 1

HCID 668294592-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5h-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-n-methyl-benzamide収率 7.4%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 3776Isopropanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
120 °C

実験手順

2-(2,5-Dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (86.3 mg, 0.290 mmol) and N*7*-(2,2,2-trifluoro-ethyl)-6,7,8,9-tetrahydro-5H-benzocycloheptene-2,7-diamine (75 mg, 0.290 mmol) were combined with DL-10-camphorsulfonic acid (101 mg, 0.436 mmol) in 2 ml IPA and heated in a microwave vial for 40 minutes at 120° C. for 40 minutes. The resulting reaction was poured into 25 ml saturated sodium bicarbonate solution and 50 ml water and extractred with 4×25 ml portions of methylene chloride. The combined organic was dried over magnesium sulfate, filtered and evaporated. The crude product was purified via reverse phase preparative chromatography (Luna C18, 5 μm, 100 mm×21.2 mm column) using a gradient of 0-35% MeCN in water (both containing 0.1% TFA). 2-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide (11.18 mg, 7.4% yield) was isolated as an off white solid. 1H-NMR (CDCl3) δ 11.07 (s, 1H), 8.66 (d, J=8.44 Hz, 1H), 7.45 (m, 2H), 7.35 (s, 1H), 7.04 (m, 2H), 6.91 (s, 1H), 6.18 (s, 1H), 3.24 (q, J=19.4, 9.8 Hz, 2H), 3.03 (d, J=4.8 Hz, 3H), 2.87 (m, 3H), 2.66 (m, 2H), 2.06 (m, 2H), 1.32 (m, 5H). LC/MS (ESI+)=519 (M+H). MP=202-203° C.

後処理

  1. customThe resulting reaction
  2. dry with materialThe combined organic was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified via reverse phase preparative chromatography (Luna C18, 5 μm, 100 mm×21.2 mm column)

出典と根拠

ORDレコード
ord-7d86cf6c388a4833b62829c151c16b3e
出典データセット
uspto-grants-2013_10
特許番号
US08552186B2

反応ノート

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