Diphenyl chlorophosphate → [4-(4-Fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl]methyl diphenyl phosphate

HRID 43240

반응식

HRID 43240 반응식
C(N(C(C)C)CC)(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:22]([CH2:23][OH:24])=[C:21]([CH:25]([CH3:27])[CH3:26])[N:20]=[C:19]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:31])=[O:30])[N:18]=2)=[CH:13][CH:12]=1.CC1C=CN=C(N)C=1C.[P:43](Cl)([O:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)([O:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:44]>ClCCl>[P:43]([O:45][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)([O:52][C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)([O:24][CH2:23][C:22]1[C:17]([C:14]2[CH:15]=[CH:16][C:11]([F:10])=[CH:12][CH:13]=2)=[N:18][C:19]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:31])=[O:30])=[N:20][C:21]=1[CH:25]([CH3:27])[CH3:26])=[O:44]

참가 물질

6

반응물 4

HCID 75654Diphenyl chlorophosphateHCID 81531DiisopropylethylamineHCID 9819937N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamideHCID 110078842-Amino-3,4-dimethylpyridine

생성물 1

HCID 67452498[4-(4-Fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl]methyl diphenyl phosphate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Diisopropyl ethyl amine (84.12 g) was slowly added to a mixture of N-[4-(4-fluorophenyl)-5-(hydroxymethyl)-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide (commercially available; 100 g) and dimethyl aminopyridine (5 g) and diphenyl chlorophosphate (123.2 g) in dichloromethane (500 mL) at 0° C. to 5° C. The reaction mixture was stirred for 30 minutes at the same temperature to give [4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl]methyl diphenyl phosphate. To this mixture was added 2-mercapto-5-methyl-1,3,4-thiadiazole (41 g) at 0° C. to 5° C. followed by slow addition of diisopropyl ethyl amine (36.5 g). The resultant mixture was stirred for 2 hours at 0° C. to 5° C. After completion of the reaction, the mixture was quenched with de-ionized water (500 mL) and acidified to pH 3.5 using hydrochloric acid (6N). The organic layer was separated and washed with sodium bicarbonate (5%) at room temperature. The organic layer was separated and dichloromethane was recovered at 45° C. to give oily residue. Methanol (300 mL) was added to resulting oily residue and the mixture was stirred at room temperature for one hour to give N-[4-(4-fluorophenyl)-5-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide, which was filtered, washed with methanol (100 mL) and dried at 45° C. for 2 hours.

후처리

  1. customat 0° C. to 5° C

출처 및 근거

ORD 기록
ord-e42b81d89ecc4e9ca1bccd8e60ef7197
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536330B2

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