Sodium Carbonate → (4-Morpholin-4-yl-phenyl)-[5-(1,1,3-trioxo-2,3-dihydro-1H-1lambda6-benzo[d]isothiazol-6-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]-carbamic acid tert-butyl ester

HRID 605930Notes

Reaction equation

HRID 605930 reaction equation
CN1CCN(C2C=CC(NC3C4N(N=CN=4)C(C4C=C(C(N)=O)SC=4)=CN=3)=CC=2)CC1.[C:32]([O:36][C:37](=[O:61])[N:38]([C:51]1[C:52]2[N:53]([N:58]=[CH:59][N:60]=2)[C:54](Br)=[CH:55][N:56]=1)[C:39]1[CH:44]=[CH:43][C:42]([N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)=[CH:41][CH:40]=1)([CH3:35])([CH3:34])[CH3:33].[O:62]=[S:63]1(=[O:82])[C:67]2[CH:68]=[C:69](B3OC(C)(C)C(C)(C)O3)[CH:70]=[CH:71][C:66]=2[C:65](=[O:81])[NH:64]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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:32]([O:36][C:37](=[O:61])[N:38]([C:39]1[CH:44]=[CH:43][C:42]([N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)=[CH:41][CH:40]=1)[C:51]1[C:52]2[N:53]([N:58]=[CH:59][N:60]=2)[C:54]([C:69]2[CH:70]=[CH:71][C:66]3[C:65](=[O:81])[NH:64][S:63](=[O:62])(=[O:82])[C:67]=3[CH:68]=2)=[CH:55][N:56]=1)([CH3:35])([CH3:34])[CH3:33]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 575899284-{8-[4-(4-Methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyrazin-5-yl}-thiophene-2-carboxylic acid amideHCID 575900981,1-Dioxo-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2-dihydro-1lambda6-benzo[d]isothiazol-3-oneHCID 86619661(5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-(4-morpholin-4-yl-phenyl)-carbamic acid tert-butyl ester

Product 1

HCID 67047387(4-Morpholin-4-yl-phenyl)-[5-(1,1,3-trioxo-2,3-dihydro-1H-1lambda6-benzo[d]isothiazol-6-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl]-carbamic acid tert-butyl esterYield 44%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

This compound may be prepared using methods as described for Compound 6, step 4 using (5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-(4-morpholin-4-yl-phenyl)-carbamic acid tert-butyl ester (170 mg, 0.36 mmol), 1,1-dioxo-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2-dihydro-1λ6-benzo[d]isothiazol-3-one (374 mg, 0.72 mmol) and Pd(PPh3)4 (100 mg, 0.082 mmol) in 1.5M Na2CO3 (2 mL, 3 mmol) and dioxane (6 mL). Purification of the reaction mixture by silica gel column chromatography using 1:1 petroleum ether:ethyl acetate affords a compound still impure. A second silica gel column chromatography eluting with 10:1 DCM:MeOH affords the title compound (91 mg, 44%).

Workup

  1. customThis compound may be prepared
  2. customPurification of the reaction mixture by silica gel column chromatography
  3. customethyl acetate affords a compound still impure
  4. washA second silica gel column chromatography eluting with 10:1 DCM

Sources & evidence

ORD record
ord-1cafade588b74db187a280969cfd95e9
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

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