Morpholine → HCID 59302981, compound

HRID 448113Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[C:19]2[N:23]([CH3:24])[C:22]([CH3:25])=[N:21][N:20]=2)(=[O:10])=[O:9])=[CH:4][C:3]=1[F:26].O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[NH:82]1[CH2:87][CH2:86][O:85][CH2:84][CH2:83]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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([NH:11][S:8]([C:5]2[CH:6]=[CH:7][C:2]([N:82]3[CH2:87][CH2:86][O:85][CH2:84][CH2:83]3)=[C:3]([F:26])[CH:4]=2)(=[O:10])=[O:9])=[C:13]([C:19]2[N:23]([CH3:24])[C:22]([CH3:25])=[N:21][N:20]=2)[CH:14]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A 25 mL scintillation vial was charged with 4-bromo-N-[4-chloro-2-(4,5-dimethyl-4H-[1,2,4]triazol-3-yl)-phenyl]-3-fluoro-benzenesulfonamide (synthesized according to general procedure C, 92 mg, 0.2 mmol), potassium phosphate monohydrate (276 mg, 1.2 mmol), BINAP (30 mg, 0.048 mmol), morpholine (87 mg, 1.0 mmol), Pd2(dba)3 (10 mg, 0.011 mmol), and DMF (2 mL). The vial was sealed and stirred at 90° C. for 20 h. The crude product was purified by flash column chromatography (10-100% ethyl acetate and hexane) followed by preparative HPLC (10-90% gradient of MeCN-water) to afford the title compound as a white solid: 1H NMR (400 MHz, CDCl3/HCl) δ 2.4 (s, 3H), 2.7-3.7 (m, 8H), 3.8 (s, 3H), 6.7 (d, 1H), 7.1-7.3 (m, 3H), 7.4 (d, 1H), 7.5 (d, 1H), MS (ES) M+H expected 466.0, found 466.0.

Workup

customThe vial was sealed
customThe crude product was purified by flash column chromatography (10-100% ethyl acetate and hexane)

Sources & evidence

ORD record: ord-ddff79795eb14cb4b5a04a34e37720bd
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481579B2

Reaction notes

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