Potassium Phosphate, Tribasic → HCID 57798003, compound

HRID 1948864Notes

Reaction equation

HRID 1948864 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[N:12]=[C:13](I)[N:14]=[CH:15][C:10]=3[CH2:9][N:8]=[C:7]([C:17]3[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=3[F:24])[C:6]=2[CH:25]=1.[NH2:26][C:27]1[O:28][C:29]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][N:31]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:35]([O:34][C:32]([C:29]1[O:28][C:27]([NH:26][C:13]2[N:14]=[CH:15][C:10]3[CH2:9][N:8]=[C:7]([C:17]4[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=4[F:24])[C:6]4[CH:25]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=4[C:11]=3[N:12]=2)=[N:31][CH:30]=1)=[O:33])[CH3:36]

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 5260193Ethyl 2-amino-1,3-oxazole-5-carboxylateHCID 86601588HCID 86601588, compound

Product 1

HCID 57798003HCID 57798003, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A mixture of 9-Chloro-7-(2,6-difluoro-phenyl)-2-iodo-5H-benzo[c]pyrimido[4,5-e]azepine (200 mg, 0.43 mmol), ethyl 2-aminooxazole-5-carboxylate (81.2 mg, 0.52 mmol), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (935 mg, 0.034 mmol), Xantphos (30 mg, 0.052 mmol), powdered K3PO4 (183 mg, 0.86 mmol), and degassed toluene were submitted to microwave irradiation (300 W) for 20 minutes at 145° C. The mixture was cooled to room temperature and then evaporated to leave a brown solid which was purified by column chromatography (silica gel, CH2Cl2 to 50% diethyl ether in CH2Cl2) to yield 2-[9-Chloro-7-(2,6-difluoro-phenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-ylamino]-oxazole-5-carboxylic acid ethyl ester as a yellow powder (103 mg, 48%) MS m/z=496 (M+H). 2-[9-Chloro-7-(2,6-difluoro-phenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-ylamino]-oxazole-5-carboxylic acid ethyl ester (91 mg, 0.18 mmol), methanol (1 mL), tetrahydrofuran (3 mL), and 1N LiOH (3.7 mL, 3.7 mmol) were stirred at room temperature for 3 hours. Water (50 mL) was added with stirring, and the resulting clear yellow solution was acidified by slowly adding 1N HCl. A yellow precipitate formed. Diethyl ether (10 mL) was added and the precipitate was collected by filtration, washed with water, diethyl ether and then dried in vacuo to yield I-364 as a yellow powder (78 mg, 93% yield) MS m/z=468 (M+H).

Workup

  1. customdegassed toluene
  2. customwere submitted to microwave irradiation (300 W) for 20 minutes at 145° C
  3. customevaporated
  4. customto leave a brown solid which
  5. customwas purified by column chromatography (silica gel, CH2Cl2 to 50% diethyl ether in CH2Cl2)

Sources & evidence

ORD record
ord-5810ab9c97f34476a9265d6f06c946ee
Source dataset
uspto-grants-2013_03
Patent number
US08399659B2

Reaction notes

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