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 575128Notes

Reaction equation

HRID 575128 reaction equation
[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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-4328c8df21ee441bb0e71b9b0228247a
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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