Cesium carbonate → ethyl 2-(2-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-4-cyclopentyl-5-hydroxyphenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate

HRID 383436Notes

Reaction equation

HRID 383436 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][CH2:9]2)[C:5]([O:13]C(OC)=O)=[CH:4][C:3]=1[NH:18][C:19]([CH:21]1[O:26][C:25]2[CH:27]=[CH:28][C:29]([C:31]#[N:32])=[CH:30][C:24]=2[N:23]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:22]1)=[O:20].CC1(C)C(C)(C)OB([C:46]2[CH2:47][CH2:48][N:49]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:50][CH:51]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.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>[C:55]([O:54][C:52]([N:49]1[CH2:48][CH:47]=[C:46]([C:2]2[CH:7]=[C:6]([CH:8]3[CH2:12][CH2:11][CH2:10][CH2:9]3)[C:5]([OH:13])=[CH:4][C:3]=2[NH:18][C:19]([CH:21]2[O:26][C:25]3[CH:27]=[CH:28][C:29]([C:31]#[N:32])=[CH:30][C:24]=3[N:23]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:22]2)=[O:20])[CH2:51][CH2:50]1)=[O:53])([CH3:58])([CH3:56])[CH3:57]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59394958HCID 59394958, compound

Product 1

HCID 59395028ethyl 2-(2-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-4-cyclopentyl-5-hydroxyphenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylateYield 56%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Ethyl 2-(2-bromo-4-cyclopentyl-5-(methoxycarbonyloxy)phenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (166 mg, 0.29 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (90 mg, 0.29 mmol), Pd(PPh3)4 (34 mg, 0.03 mmol), and Cs2CO3 (189 mg, 0.58 mmol) were combined in DMF (4 mL) and heated at 90° C. for 4 h. The reaction was quenched with water (50 mL) and extracted with dichloromethane (3×10 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (0-100% ethyl acetate/hexanes) yielded ethyl 2-(2-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-4-cyclopentyl-5-hydroxyphenylcarbamoyl)-6-cyano-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (100 mg, 56% yield). LC/MS m/z 617.4 [M+H]+.

Workup

  1. customThe reaction was quenched with water (50 mL)
  2. extractionextracted with dichloromethane (3×10 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-02f5aa775b2d491cb57053fb0cc662bd
Source dataset
uspto-grants-2013_02
Patent number
US08367660B2

Reaction notes

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