Isopropanol → 2-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide

HRID 1040703ノート

反応式

HRID 1040703 の反応式
[F:1][C:2]1([F:14])[CH2:8][CH2:7][C:6]2[CH:9]=[C:10]([NH2:13])[CH:11]=[CH:12][C:5]=2[CH2:4][CH2:3]1.Cl[C:16]1[N:21]=[C:20]([NH:22][C:23]2[CH:32]=[CH:31][CH:30]=[CH:29][C:24]=2[C:25]([NH:27][CH3:28])=[O:26])[C:19]([Cl:33])=[CH:18][N:17]=1.C(O)(C)C.Cl.O1CCOCC1>>[Cl:33][C:19]1[C:20]([NH:22][C:23]2[CH:32]=[CH:31][CH:30]=[CH:29][C:24]=2[C:25]([NH:27][CH3:28])=[O:26])=[N:21][C:16]([NH:13][C:10]2[CH:11]=[CH:12][C:5]3[CH2:4][CH2:3][C:2]([F:14])([F:1])[CH2:8][CH2:7][C:6]=3[CH:9]=2)=[N:17][CH:18]=1

参加物

5

反応物 4

HCID 3776IsopropanolHCID 204431481,4-Dioxane hydrochlorideHCID 578538657,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamineHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamide

生成物 1

HCID 668295302-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide収率 29%

実験手順

Into a microwave vial was placed 7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamine (79 mg, 0.00040 mol) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (100 mg, 0.0003 mol) in isopropyl alcohol (4 mL, 0.05 mol). 4N HCl-dioxane (0.04 g, 0.0003 mol;) was added to the reaction mixture and the contents subjected to microwaves at 120° C. for 10 min. The reaction mixture was resubjected to the same microwave conditions for an additional 10 min. A solid had precipitated out of the reaction mixture, was collected by filtration then redissolved in methylene chloride (6 mL) and washed with sat. aqueous sodium bicarbonate (1×5 mL) and water (2×5 mL). The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo to give 2-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide as a brown solid (38 mg, 29%). MP: 160-168° C.; 1HNMR (400 MHz, DMSO-d6) δ 11.59 (s, 1H), 9.46 (s, 1H), 8.80 (d, 1H, J=4.5 Hz), 8.74 (d, 1H, J=7.6), 8.26 (s, 1H), 7.79 (d, 1H, J=7.8 Hz), 7.61 (s, 1H), 7.53 (t, 1H, J=7.6), 7.45 (d, 1H, J=7.8), 7.2 (t, 1H, J=7.3), 2.85 (d, 3H, J=4 Hz), 2.69-2.77 (m, 4H), 2.06 (m, 4H); MS (m/e) 458 (M+1).

後処理

  1. waitThe reaction mixture was resubjected to the same microwave conditions for an additional 10 min
  2. customA solid had precipitated out of the reaction mixture
  3. filtrationwas collected by filtration
  4. dissolutionthen redissolved in methylene chloride (6 mL)
  5. washwashed with sat. aqueous sodium bicarbonate (1×5 mL) and water (2×5 mL)
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-add57fe2d4ab480892301b7da3af8ae5
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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