6-(5-(Methylsulfonyl)-1,3,4-thiadiazol-2-yl)isoquinoline → (+/-)-N-(2-(tert-butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine

HRID 2075343ノート

反応式

HRID 2075343 の反応式
[Si:1]([O:8][CH:9]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH:13]=1)[CH2:10][NH2:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CS([C:30]1[S:34][C:33]([C:35]2[CH:36]=[C:37]3[C:42](=[CH:43][CH:44]=2)[CH:41]=[N:40][CH:39]=[CH:38]3)=[N:32][N:31]=1)(=O)=O.CS(C1SC(C2C=C3C(=CC=2)C=NC=C3)=NN=1)=O>CC(N(C)C)=O>[Si:1]([O:8][CH:9]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:20])[CH3:21])[CH:13]=1)[CH2:10][NH:11][C:30]1[S:34][C:33]([C:35]2[CH:36]=[C:37]3[C:42](=[CH:43][CH:44]=2)[CH:41]=[N:40][CH:39]=[CH:38]3)=[N:32][N:31]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 579918986-(5-(Methylsulfonyl)-1,3,4-thiadiazol-2-yl)isoquinolineHCID 57991914(+/-)-2-(tert-Butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethanamineHCID 670894316-(5-(Methylsulfinyl)-1,3,4-thiadiazol-2-yl)isoquinoline

生成物 1

HCID 67089325(+/-)-N-(2-(tert-butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

実験手順

(±)-2-(tert-Butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethanamine and 6-(5-(methylsulfonyl)-1,3,4-thiadiazol-2-yl)isoquinoline and 6-(5-(methylsulfinyl)-1,3,4-thiadiazol-2-yl)isoquinoline (prepared as in Scheme 7) was heated at 80-100° C. for 3 hours in DMA (0.3 M) to provide (±)-N-(2-(tert-butyldimethylsilyloxy)-2-(3-(tert-butyldimethylsilyloxy)phenyl)ethyl)-5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine. This intermediate was dissolved in THF and TBAF (1M in THF, 1.24 mmol) was added. After 16 hours, the mixture was concentrated in vacuo and the residue purified by flash chromatography on silica (eluting with DCM/MeOH gradients) to provide (±)-3-(1-hydroxy-2-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-ylamino)ethyl)phenol (20 mg, 8%). LCMS (M+H) 365 calc. for C19H17N4O2S 365.1. 1H NMR (300 MHz, DMSO-d6): δ ppm 9.33 (s, 1H+OH), 8.56 (d, J=5.8 Hz, 1H), 8.27 (m, 2H), 8.18 (m, 2H), 7.92 (d, J=5.8 Hz, 1H), 7.14 (t, J=7.6, 1H), 6.84 (m, 2H), 6.65 (m, 1H), 5.58 (d, J=4.0 Hz, OH), 4.80 (m, 1H), 3.60 (m, 1H). 1H missing, covered by water signal.

出典と根拠

ORDレコード
ord-7782da3070134df0933637d4b9e1e081
出典データセット
uspto-grants-2011_04
特許番号
US07919504B2

反応ノート

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