2-Nitro-8,9-dihydro-5H-benzo[7]annulen-7(6H)-one → (1S,2S,3R,4R)-3-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide

HRID 1041225ノート

反応式

HRID 1041225 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7][C:6]=2[CH:13]=1.ClC1N=C(NC2C=CC=CC=2C2N(C)C=CN=2)C(Cl)=CN=1.Cl[C:36]1[N:41]=[C:40]([NH:42][C@@H:43]2[C@@H:48]3[CH2:49][C@@H:45]([CH:46]=[CH:47]3)[C@@H:44]2[C:50]([NH2:52])=[O:51])[C:39]([Cl:53])=[CH:38][N:37]=1.[N+](C1C=CC2CCC(=O)CCC=2C=1)([O-])=O>>[Cl:53][C:39]1[C:40]([NH:42][C@@H:43]2[C@@H:48]3[CH2:49][C@@H:45]([CH:46]=[CH:47]3)[C@@H:44]2[C:50]([NH2:52])=[O:51])=[N:41][C:36]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7][C:6]=3[CH:13]=2)=[N:37][CH:38]=1

参加物

5

反応物 4

HCID 457903192-Nitro-8,9-dihydro-5H-benzo[7]annulen-7(6H)-oneHCID 57522618HCID 57522618、化合物HCID 672635032-Amino-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol2 回HCID 86633891(2,5-Dichloro-pyrimidin-4-yl)-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-amine

生成物 1

HCID 67264345(1S,2S,3R,4R)-3-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide

実験手順

Prepared analogously to Example 216d replacing 3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine with 2-Amino-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol and (2,5-Dichloro-pyrimidin-4-yl)-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-amine was replaced with (1S,2S,3R,4R)-3-(2,5-Dichloro-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide. 2-Amino-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol is a byproduct from the reductive amination of 2-Nitro-5,6,8,9-tetrahydro-benzocyclohepten-7-one with various amines. The reaction was carried out in the presence of the desired reductive amination product to provide a crude mixture of amino and alcohol products. The crude mix was then reduced and a mixture of amino and alcohol products were used in the synthesis of target compounds. The mixture was then purified by prep HPLC to afford the desired amino compound as well as (1S,2S,3R,4R)-3-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide. LC/MS (ESI): 440.22. 1H NMR (400 MHz, DMSO, d6) δ 9.12 (s, 1H), 7.93 (s, 1H), 7.78 (s, 1H), 7.69 (m, 1H), 7.46 (m, 2H), 7.26 (s, 1H), 6.97 (d, 1H, J=8.08 Hz), 6.35 (m, 1H), 6.27 (m, 1H), 4.58 (m, 1H), 4.15 (m, 1H), 3.72 (m, 1H), 3.31 (s, 2H), 2.88 (s, 1H), 2.78 (m, 3H), 2.11 (d, 1H, J=8.59 Hz), 1.89 (m, 2H), 1.41 (d, 1H, J=8.09 Hz), 1.33 (m, 2H).

後処理

  1. customPrepared analogously to Example 216d
  2. customto provide a crude
  3. additionThe crude mix
  4. customwere used in the synthesis of target compounds
  5. customThe mixture was then purified by prep HPLC

出典と根拠

ORDレコード
ord-95bf4c12593b413fa7657648e7992883
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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