Water → HCID 178502377、化合物

HRID 1776013ノート

反応式

HRID 1776013 の反応式
C(OC([NH:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1)=O)C1C=CC=CC=1.[CH3:21][O:22][C:23](=[O:48])[NH:24][C@H:25]([C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:46]=[CH:45][C:44](Br)=[CH:43][CH:42]=2)[N:40]=1)=[O:30])[CH:26]([CH3:28])[CH3:27].CN(C)C=O.O.C(=O)(O)[O-].[Na+]>CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[OH-].[Pd+2]>[CH3:21][O:22][C:23](=[O:48])[NH:24][C@H:25]([C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:42]=[CH:43][C:44]([C:15]3[CH:14]=[CH:13][C:12]([NH2:11])=[CH:17][CH:16]=3)=[CH:45][CH:46]=2)[N:40]=1)=[O:30])[CH:26]([CH3:28])[CH3:27]

参加物

9

反応物 5

HCID 962WaterHCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 27733224-(Benzyloxycarbonylamino)phenylboronic Acid (contains varying amounts of Anhydride)HCID 178502354HCID 178502354、化合物

生成物 1

HCID 178502377HCID 178502377、化合物収率 38.2%

試薬・触媒・溶媒 3

HCID 9942167Palladium hydroxide触媒HCID 178418397HCID 178418397、化合物触媒HCID 887Methanol溶媒

反応条件

温度
90 °C

実験手順

To a mixture of 4-(benzyloxycarbonylamino)phenylboronic acid (1.57 g, 5.79 mmol) and ((S)-1-{(S)-2-[4-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (1.74 g, 3.86 mmol) in N,N-dimethylformamide (30 mL, 400 mmol) was added water (21.91 mL, 1216 mmol) and sodium bicarbonate (2.43 g, 28.96 mmol). The resulting mixture was purged with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (468 mg, 0.41 mmol) was added. The reaction mixture was purged with nitrogen and then heated at 90° C. overnight. The reaction mixture was cooled to RT, diluted with methanol (10 mL), then filtered. The filtrate was concentrated and the crude product was purified by preparative HPLC to give a white solid. (1.28 g) The crude material was dissolved in methanol (40 mL) and then pumped through a continuous flow hydrogenator at 70° C. using a palladium hydroxide on carbon (20% w/w) cartridge. The resulting solution was concentrated to ˜10 mL, treated with Stratospheres™ PL-CO3 resin and stirred at room temperature for 30 min. The reaction mixture was filtered and the filtrate was concentrated to give the title compound (680 mg).

後処理

  1. customThe resulting mixture was purged with nitrogen
  2. customThe reaction mixture was purged with nitrogen
  3. temperatureThe reaction mixture was cooled to RT
  4. additiondiluted with methanol (10 mL)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customthe crude product was purified by preparative HPLC
  8. customto give a white solid
  9. custompumped through a continuous flow hydrogenator at 70° C.
  10. concentrationThe resulting solution was concentrated to ˜10 mL
  11. additiontreated with Stratospheres™ PL-CO3 resin
  12. filtrationThe reaction mixture was filtered
  13. concentrationthe filtrate was concentrated

出典と根拠

ORDレコード
ord-e254abc3d15b415396423174325d9348
出典データセット
uspto-grants-2016_02
特許番号
US09260414B2

反応ノート

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