Potassium Carbonate → HCID 25171866, compound

HRID 2093610Notes

Reaction equation

HRID 2093610 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]([C:9]1[CH:10]=[C:11]([CH:35]([CH3:37])[CH3:36])[C:12]2[O:16][C:15]([C:17]3[CH:33]=[CH:32][C:20]([C:21]([NH:23][CH2:24][C@H:25]4[O:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)=[O:22])=[CH:19][CH:18]=3)=[N:14][C:13]=2[CH:34]=1)#[N:8].Br[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([C:46]([F:49])([F:48])[F:47])[CH:41]=1>CO>[C:7]([C:9]1[CH:10]=[C:11]([CH:35]([CH3:37])[CH3:36])[C:12]2[O:16][C:15]([C:17]3[CH:33]=[CH:32][C:20]([C:21]([NH:23][CH2:24][C@H:25]4[O:31][CH2:30][CH2:29][N:28]([CH2:39][C:40]5[CH:45]=[CH:44][CH:43]=[C:42]([C:46]([F:47])([F:48])[F:49])[CH:41]=5)[CH2:27][CH2:26]4)=[O:22])=[CH:19][CH:18]=3)=[N:14][C:13]=2[CH:34]=1)#[N:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1230611-(Bromomethyl)-3-(trifluoromethyl)benzeneHCID 68742534HCID 68742534, compound2×

Product 1

HCID 25171866HCID 25171866, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 36 mg of potassium carbonate in methanol (3 ml) was added 37 mg of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-[(7S)-1,4-oxazepan-7-ylmethyl]benzamide (INTERMEDIATE 20) followed by 1-(bromomethyl)-3-(trifluoromethyl)benzene (13 μl). The mixture was heated to 70° C. and stirred for 8 h, and then cooled and added directly to a 40M samplet for purification via column chromatography on a Biotage Horizon 40M column, eluting with 1 column volume of 100% hexanes, followed by a gradient of 0 to 100% ethyl acetate in hexanes over 10 column volumes, followed by 4 column volumes of 100% ethyl acetate, to provide the title compound (28 mg, 56%). Mass spectrum (ESI) 577.2 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.33 (d, J=8.4 Hz, 2H), 7.96 (d, J=6.0 Hz, 2H), 7.94 (s, 1H), 7.61 (s, 1H), 7.52 (m, 3H), 7.44 (t, J=7.5 Hz, 1H), 6.65 (bs, 1H), 3.96 (m, 2H), 3.81 (m, 2H), 3.70 (s, 2H), 3.68 (m, 2H), 3.48 (sept, J=7.0 Hz, 1H), 3.25 (m, 1H), 2.74 (m, 2H), 2.01 (m, 1H), 1.82 (m, 1H), 1.46 (d, J=7.0 Hz, 6H).

Workup

  1. temperaturecooled
  2. additionadded directly to a 40M
  3. customsamplet for purification via column chromatography on a Biotage Horizon 40M column
  4. washeluting with 1 column volume of 100% hexanes

Sources & evidence

ORD record
ord-c5d74f1ce9114411b360feb387f9d255
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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