Di-tert-butyl [5-(5-chloro-2-{4-[(2,4-dimethoxybenzyl)(1,2,4-thiadiazol-5-yl)sulfamoyl]-2,5-difluorophenoxy}phenyl)-1,2-benzoxazol-3-yl]imidodicarbonate → 4-(4-chloro-2-(3-(methylamino)benzo[d]isoxazol-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

HRID 2203438Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:32][C:33]2[CH:38]=[C:37]([F:39])[C:36]([S:40](=[O:59])(=[O:58])[N:41](CC3C=CC(OC)=CC=3OC)[C:42]3[S:46][N:45]=[CH:44][N:43]=3)=[CH:35][C:34]=2[F:60])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][N:14]=[C:13]([N:16](C(OC(C)(C)C)=O)[C:17](OC(C)(C)C)=O)[C:12]=3[CH:31]=2)[CH:7]=1.ClC1C=CC(OC2C=C(F)C(S(=O)(=O)N(CC3C=CC(OC)=CC=3OC)C3SN=CN=3)=CC=2F)=C(C2C=CC3ON=C(N(C)C(=O)OC(C)(C)C)C=3C=2)C=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:32][C:33]2[C:34]([F:60])=[CH:35][C:36]([S:40]([NH:41][C:42]3[S:46][N:45]=[CH:44][N:43]=3)(=[O:59])=[O:58])=[C:37]([F:39])[CH:38]=2)=[C:6]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][N:14]=[C:13]([NH:16][CH3:17])[C:12]=3[CH:31]=2)[CH:7]=1

Participants

Reactant 2

HCID 123740120Di-tert-butyl [5-(5-chloro-2-{4-[(2,4-dimethoxybenzyl)(1,2,4-thiadiazol-5-yl)sulfamoyl]-2,5-difluorophenoxy}phenyl)-1,2-benzoxazol-3-yl]imidodicarbonate

HCID 131735789tert-butyl (5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-phenyl)benzo[d]isoxazol-3-yl)(methyl)carbamate

Product 1

HCID 715589174-(4-chloro-2-(3-(methylamino)benzo[d]isoxazol-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideYield 75%

Procedure

Following the procedure as described in EXAMPLE 44, making non-critical variations to replace di-tert-butyl [5-(5-chloro-2-{4-[(2,4-dimethoxybenzyl)(1,2,4-thiadiazol-5-yl)sulfamoyl]-2,5-difluorophenoxy}phenyl)-1,2-benzoxazol-3-yl]imidodicarbonate with tert-butyl (5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)(methyl)carbamate, 4-(4-chloro-2-(3-(methylamino)benzo[d]isoxazol-5-yl)phenoxy)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide was obtained as an off-white solid in 75% yield over two steps (0.21 g): 1H NMR (300 MHz, DMSO-d6) δ8.52 (s, 1H), 7.95 (d, J=1.1 Hz, 1H), 7.72 (dd, J=9.9, 6.5 Hz, 1H), 7.65 (dd, J=8.7, 1.6 Hz, 1H), 7.61 (d, J=2.6 Hz, 1H), 7.52-7.46 (m, 2H), 7.28 (d, J=8.7 Hz, 1H), 7.14 (dd, J=10.4, 6.5 Hz, 1H), 7.04-6.97 (m, 1H), 2.86 (s, 3H), (NH not observed); MS (ES+) m/z 549.6 (M+1), 551.6 (M+1).

Sources & evidence

ORD record: ord-a3e205504a1045da9843185a693607df
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365578B2

Reaction notes

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