4-Methylmorpholine → 1h-Pyrrolo[2,3-c]pyridine-5-carboxamide,1-[(2,4-difluorophenyl)methyl]-n-hydroxy-3-[(2-methoxyethoxy)methyl]-n-methyl-

HRID 2377120ノート

反応式

HRID 2377120 の反応式
[F:1][C:2]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([OH:16])=O)[CH:13]=[C:8]2[C:7]([CH2:17][O:18][CH2:19][CH2:20][O:21][CH3:22])=[CH:6]1.CN1CCOCC1.Cl.[CH3:36][NH:37][OH:38]>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([N:37]([OH:38])[CH3:36])=[O:16])[CH:13]=[C:8]2[C:7]([CH2:17][O:18][CH2:19][CH2:20][O:21][CH3:22])=[CH:6]1

参加物

6

反応物 3

HCID 79724-MethylmorpholineHCID 77906N-methylhydroxylamine hydrochlorideHCID 598558181h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(2,4-difluorophenyl)methyl]-3-[(2-methoxyethoxy)methyl]-

生成物 1

HCID 159570881h-Pyrrolo[2,3-c]pyridine-5-carboxamide,1-[(2,4-difluorophenyl)methyl]-n-hydroxy-3-[(2-methoxyethoxy)methyl]-n-methyl-収率 66%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
4 °C

実験手順

To a solution of 1-(2,4-difluorobenzyl)-3-[(2-methoxyethoxy)methyl]-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid 782 mg 2.078 mmol) in anhydrous DMF (10 ml) was added CDMT (438 mg 2.439 mmol 1.2 eq.) and NMM (N-methyl morpholine) (0.28 ml 2.493 mmol 1.2 eq.). The mixture, under nitrogen, was stirred for 2.0 hours, during which it slowly darkened to a deep orange. N-Methylhydroxylamine hydrochloride (868 mg 10.389 mmol 5.0 eq) was added and stirring continued for 10 hours. The reaction was judged to be complete by HPLC-MS analysis and the volatiles were removed in vacuo (ca. 2 torr) to give a golden yellow oil. This oil was dissolved in EtOAc (30 mL) and washed with water (3×20 mL) and brine (20 mL). The organic phase was separated, dried (Na2SO4), and concentrated in vacuo to afford the crude product which was purified by recrystallisation in hot IPA (20 ml) with cooling at 4° C. overnight to give 556 mg (66%) of 1-(2,4-difluorobenzyl)-N-hydroxy-3-[(2-methoxyethoxy)methyl]-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide as a pale tan powder. LC-MS (Eclipse XDB-C8, 0.8 mL/min, gradient 80:20 to 5:95H2O (+0.1% HOAc):CH3CN—3 minutes, APCI, +mode): RT—1.08 min, m/e=344.2 (M+H+, base).

後処理

  1. stirringstirring
  2. waitcontinued for 10 hours
  3. customthe volatiles were removed in vacuo (ca. 2 torr)
  4. customto give a golden yellow oil
  5. washwashed with water (3×20 mL) and brine (20 mL)
  6. customThe organic phase was separated
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto afford the crude product which
  10. customwas purified by recrystallisation in hot IPA (20 ml)

出典と根拠

ORDレコード
ord-8cd0172120c24b19a3853f61b1dca4ec
出典データセット
uspto-grants-2008_12
特許番号
US07468375B2

反応ノート

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