Acetic Acid → 3-{1-[6-(2-cyclopropylmethyl-7-methyl-3H-benzimidazol-5-yloxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

HRID 1846543ノート

反応式

HRID 1846543 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH:32]=[C:33]([CH3:36])[C:34]=1[NH2:35])[O:5][C:6]1[N:11]=[CH:10][N:9]=[C:8]([N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[CH2:24][CH2:23][C:22]4[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:21]=4[NH:20][C:19]3=[O:31])[CH2:14][CH2:13]2)[CH:7]=1.[CH:37]1([CH2:40][C:41](O)=O)[CH2:39][CH2:38]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O)(=O)C>CN(C=O)C>[CH:37]1([CH2:40][C:41]2[NH:1][C:2]3[CH:3]=[C:4]([O:5][C:6]4[N:11]=[CH:10][N:9]=[C:8]([N:12]5[CH2:13][CH2:14][CH:15]([N:18]6[CH2:24][CH2:23][C:22]7[CH:25]=[C:26]([O:29][CH3:30])[CH:27]=[CH:28][C:21]=7[NH:20][C:19]6=[O:31])[CH2:16][CH2:17]5)[CH:7]=4)[CH:32]=[C:33]([CH3:36])[C:34]=3[N:35]=2)[CH2:39][CH2:38]1

参加物

6

反応物 4

HCID 176Acetic AcidHCID 138440Cyclopropaneacetic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 669783753-{1-[6-(3,4-Diamino-5-methyl-phenoxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

生成物 1

HCID 462446763-{1-[6-(2-cyclopropylmethyl-7-methyl-3H-benzimidazol-5-yloxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

0.20 g (0.42 mmol) 3-{1-[6-(3,4-diamino-5-methyl-phenoxy)-pyrimidin-4-yl]-piperidin-4-yl}-7-methoxy-1,3,4,5-tetrahydro-benzo[d][1,3]diazepin-2-one, 46 mg (0.46 mmol) cyclopropyl-acetic acid, 151 mg (0.47 mmol) TBTU and 0.14 mL (1.00 mmol) TEA in 2.00 mL DMF were stirred for 4 h at RT. Then 2.00 mL glacial acetic acid was added and the mixture was stirred overnight at RT. In addition the reaction mixture was stirred for 1 h at 100° C., then cooled and purified by preparative HPLC-MS. The product-containing fractions were combined and the acetonitrile was evaporated down. The residue was made alkaline with 4N aqueous sodium hydroxide solution, the precipitate formed was suction filtered, washed with water and dried under HV.

後処理

  1. additionIn addition the reaction mixture
  2. stirringwas stirred for 1 h at 100° C.
  3. temperaturecooled
  4. custompurified by preparative HPLC-MS
  5. customthe acetonitrile was evaporated down
  6. customthe precipitate formed
  7. filtrationfiltered
  8. washwashed with water
  9. customdried under HV

出典と根拠

ORDレコード
ord-cbba410d95704ec09917d0c24ee01f0d
出典データセット
uspto-grants-2015_02
特許番号
US08952014B2

反応ノート

読み込み中…