Sodium Carbonate → n-{4-[4-Amino-7-(6-methoxy-3-pyridinyl)thieno[3,2-c]pyridin-3-yl]-2-methoxyphenyl}-1-methyl-1h-indole-2-carboxamide

HRID 1270876ノート

反応式

HRID 1270876 の反応式
Br[C:2]1[C:6]2[C:7]([NH2:19])=[N:8][CH:9]=[C:10]([C:11]3[CH:12]=[N:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=3)[C:5]=2[S:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:24][C:23]=1[NH:37][C:38]([C:40]1[N:41]([CH3:49])[C:42]2[C:47]([CH:48]=1)=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.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>[NH2:19][C:7]1[C:6]2[C:2]([C:26]3[CH:25]=[CH:24][C:23]([NH:37][C:38]([C:40]4[N:41]([CH3:49])[C:42]5[C:47]([CH:48]=4)=[CH:46][CH:45]=[CH:44][CH:43]=5)=[O:39])=[C:22]([O:21][CH3:20])[CH:27]=3)=[CH:3][S:4][C:5]=2[C:10]([C:11]2[CH:12]=[N:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)=[CH:9][N:8]=1

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 184507873-Bromo-7-(6-methoxypyridin-3-yl)thieno[3,2-c]pyridin-4-amineHCID 22347095N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide

生成物 1

HCID 18451283n-{4-[4-Amino-7-(6-methoxy-3-pyridinyl)thieno[3,2-c]pyridin-3-yl]-2-methoxyphenyl}-1-methyl-1h-indole-2-carboxamide

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

A mixture of Example 215 (1.0 eq) in 1,2-dimethoxyethane (10 mL) and water (5 mL) was reacted with N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-indole-2-carboxamide (1.2 eq), Na2CO3 (2.4 eq), and Pd(PPh3)4 (0.06 eq) at 95° C. for 18 hours. The organic solvent was removed in vacuo and the the mixture was extracted with dichloromethane. The extract was dried (MgSO4), filtered, and concentrated. The residue was purified by preparative reverse phase HPLC (Rainin C18, 8 mm, 300 Å, 25 cm; 40% acetonitrile/0.1M ammonium acetate isocratic for 5 minutes, then 40–100% acetonitrile/0.1M ammonium acetate over 30 minutes, 21 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyophilized to provide the desired product. 1H NMR (DMSO-d6, 400 MHz) δ 9.52 (s, 1H), 8.45 (s, 1H), 8.02 (t, 1H), 7.91 (s, 1H), 7.71 (d, 1H), 7.55–7.63 (m, 2H), 7.28–7.38 (m, 2H), 7.23 (s, 1H), 7.08–7.18 (m, 2H), 7.03 (d, 1H), 5.57–5.69 (br s, 2H), 4.04 (s, 3H), 3.93 (s, 3H), 3.92 (s, 3H); reverse phase HPLC (Delta Pak C18, 5 μm, 300 Å, 15 cm; 50%-100% acetonitrile/0.1M ammonium acetate over 10 min, 1 mL/min) Rt=9.30 min.; MS m/e 536 (M+H)+.

後処理

  1. customThe organic solvent was removed in vacuo
  2. extractionthe the mixture was extracted with dichloromethane
  3. dry with materialThe extract was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative reverse phase HPLC (Rainin C18, 8 mm, 300 Å, 25 cm
  7. wait40–100% acetonitrile/0.1M ammonium acetate over 30 minutes
  8. customThe acetonitrile was removed in vacuo

出典と根拠

ORDレコード
ord-ec7c9c5d50d2482db595d15324cd2a3a
出典データセット
uspto-grants-2007_04
特許番号
US07202363B2

反応ノート

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