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 1687289ノート

反応式

HRID 1687289 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.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

7

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 2

HCID 962Water溶媒HCID 3776Isopropanol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 extracted 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. extractionextracted with 4×25 ml portions of methylene chloride
  3. dry with materialThe combined organic was dried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. 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-baa614e000c84b31ab95875de828c0ca
出典データセット
uspto-grants-2012_04
特許番号
US08148391B2

反応ノート

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