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 575128노트

반응식

HRID 575128 반응식
[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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-4328c8df21ee441bb0e71b9b0228247a
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034866B2

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