1,2-Dimethoxyethane → 6-Chloro-11-phenyl-15-oxa-2,4,8,25-tetraazatetracyclo[17.3.1.1(3,7).1(10,14)]pentacosa-1(23),3(25),4,6,10(24),11,13,19,21-nonaene

HRID 1614972Notes

Reaction equation

HRID 1614972 reaction equation
Br[C:2]1[C:3]2[CH2:4][NH:5][C:6]3[N:26]=[C:10]([NH:11][C:12]4[CH:13]=[CH:14][CH:15]=[C:16]([CH:25]=4)[CH2:17][CH2:18][CH2:19][O:20][C:21]([CH:24]=2)=[CH:22][CH:23]=1)[N:9]=[CH:8][C:7]=3[Cl:27].[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>O.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>[Cl:27][C:7]1[CH:8]=[N:9][C:10]2[NH:11][C:12]3[CH:13]=[CH:14][CH:15]=[C:16]([CH:25]=3)[CH2:17][CH2:18][CH2:19][O:20][C:21]3[CH:24]=[C:3]([CH2:4][NH:5][C:6]=1[N:26]=2)[C:2]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[CH:23][CH:22]=3

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 4686474711-Bromo-6-chloro-15-oxa-2,4,8,25-tetraazatetracyclo[17.3.1.1(3,7).1(10,14)]pentacosa-1(23),3(25),4,6,10(24),11,13,19,21-nonaene

Product 1

HCID 468647486-Chloro-11-phenyl-15-oxa-2,4,8,25-tetraazatetracyclo[17.3.1.1(3,7).1(10,14)]pentacosa-1(23),3(25),4,6,10(24),11,13,19,21-nonaeneYield 27%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of 11-bromo-6-chloro-15-oxa-2,4,8,25-tetraazatetracyclo[17.3.1.1(3,7).1(10,14)]pentacosa-1(23),3(25),4,6,10(24),11,13,19,21-nonaene (30.0 mg, 0.067 mmol) (prepared according to Example 14, Step E), phenylboronic acid (9.8 mg, 0.081 mmol), tetrakis(triphenylphosphine)palladium(0) (7.8 mg, 0.0067 mmol), 1,2-dimethoxyethane (0.50 mL), and a solution of sodium carbonate in water (0.17 mL, 2.0 M) was sealed into a microwave vial and the resultant suspension was de-gassed by bubbling with N2. After degassing, the vial was microwaved at 150° C. for 20 min. The reaction mixture was diluted with EtOAc, filtered, and concentrated to give a residue, which was purified by silica gel column chromatography to provide the desired product (8 mg, 27%) as a white powder. LCMS for C26H23ClN4O (M+H)+: m/z=443.1. 1H NMR (400 MHz, DMSO-d6): δ 8.96 (s, 1H), 7.78 (s, 1H), 7.56 (s, 1H), 7.41 (dd, J=6.0, 1.2 Hz, 2H), 7.32 (m, 2H), 7.14 (m, 1H), 7.05 (m, 1H), 6.96 (m, 1H), 6.87 (m, 2H), 6.75 (m, 1H), 5.70 (t, 2H), 4.62 (m, 2H), 4.16 (m, 1H), 4.04 (m, 1H), 2.68 (m, 2H), 1.84 (m, 2H).

Workup

  1. customthe resultant suspension was de-gassed
  2. customby bubbling with N2
  3. customAfter degassing
  4. customthe vial was microwaved at 150° C. for 20 min
  5. additionThe reaction mixture was diluted with EtOAc
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a residue, which
  9. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a44837db1de146db9f89bf8f627703f9
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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