Potassium Carbonate → (+/-) 10-(4-Fluoro-3-hydroxy-3-methyl-but-1-ynyl)-3-(morpholinomethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide

HRID 575128ノート

反応式

HRID 575128 の反応式
[F:1][CH2:2][C:3]([CH3:14])([OH:13])[C:4]#[C:5][Si](CC)(CC)CC.[C:15](=[O:18])([O-])[O-].[K+].[K+].C(=O)([O-])[O-].Br[C:26]1[CH:27]=[CH:28][C:29]2[O:35][CH2:34][CH2:33][N:32]3[C:36]([CH2:42][N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[C:37]([C:39]([NH2:41])=[O:40])[N:38]=[C:31]3[C:30]=2[CH:49]=1>CO>[F:1][CH2:2][C:3]([OH:13])([CH3:14])[C:4]#[C:5][C:26]1[CH:27]=[CH:28][C:29]2[O:35][CH2:34][CH2:33][N:32]3[C:36]([CH2:42][N:43]4[CH2:44][CH2:45][O:46][CH2:47][CH2:48]4)=[C:37]([C:39]([NH2:41])=[O:40])[N:38]=[C:31]3[C:30]=2[CH:49]=1.[OH:13][C:3]([CH3:14])([CH2:2][O:18][CH3:15])[C:4]#[C:5][C:26]1[CH:27]=[CH:28][C:29]2[O:35][CH2:34][CH2:33][N:32]3[C:36]([CH2:42][N:43]4[CH2:44][CH2:45][O:46][CH2:47][CH2:48]4)=[C:37]([C:39]([NH2:41])=[O:40])[N:38]=[C:31]3[C:30]=2[CH:49]=1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 19660Carbonate IonHCID 86693093Fluoro-2-methyl-4-triethylsilyl-but-3-yn-2-olHCID 8669312110-Bromo-3-(morpholinomethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide

生成物 2

HCID 71715338(+/-) 10-(4-Fluoro-3-hydroxy-3-methyl-but-1-ynyl)-3-(morpholinomethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamideHCID 8669315310-(3-Hydroxy-4-methoxy-3-methyl-but-1-ynyl)-3-(morpholinomethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

Fluoro-2-methyl-4-triethylsilyl-but-3-yn-2-ol (80 mg) was stirred for 24 hrs at room temperature with potassium carbonate (3 eq) in Methanol (1 mL) after which the carbonate was filtered and the resulting methanol was dried down to a viscous oil. This intermediate 1-fluoro-2-methyl-but-3-yn-2-ol was reacted (in accordance with a procedure described in Procedure E) with 10-bromo-3-(morpholinomethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide (30 mg) to afford 1.9 mg of (±) 10-(4-fluoro-3-hydroxy-3-methyl-but-1-ynyl)-3-(morpholinomethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide [MS (Q1) 429 (M)+] and 6.4 mg of (±) 10-(3-hydroxy-4-methoxy-3-methyl-but-1-ynyl)-3-(morpholinomethyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide [MS (Q1) 441 (M)+]. 1H NMR (400 MHz, DMSO) δ 8.49 (d, J=2.1 Hz, 1H), 7.56 (s, 1H), 7.29 (dd, J=8.5, 2.2 Hz, 1H), 7.10 (s, 1H), 7.02 (d, J=8.5 Hz, 1H), 5.53 (s, 1H), 4.54-4.42 (m, 5H), 3.98 (s, 2H), 3.57-3.48 (m, 6H), 3.37 (s, 4H), 2.41-2.37 (m, 4H), 1.43 (s, 4H)] following reverse phase purification.

後処理

  1. filtrationwas filtered
  2. dry with materialthe resulting methanol was dried down to a viscous oil
  3. customThis intermediate 1-fluoro-2-methyl-but-3-yn-2-ol was reacted (in accordance with a procedure

出典と根拠

ORDレコード
ord-4328c8df21ee441bb0e71b9b0228247a
出典データセット
uspto-grants-2015_05
特許番号
US09034866B2

反応ノート

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