Potassium Carbonate → (R)-tert-Butyl 4-fluoro-2-(4-(8-fluorochroman-4-ylamino)-5-nitropyrimidin-2-ylamino)phenylcarbamate

HRID 1363170노트

반응식

HRID 1363170 반응식
Cl.[F:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[O:11][CH2:10][CH2:9][C@H:8]2[NH2:13].C(=O)([O-])[O-].[K+].[K+].[F:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[C:23]([NH:35][C:36]2[N:41]=[C:40](SC#N)[C:39]([N+:45]([O-:47])=[O:46])=[CH:38][N:37]=2)[CH:22]=1>CS(C)=O.C(#N)C>[F:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[C:23]([NH:35][C:36]2[N:37]=[C:38]([NH:13][C@H:8]3[C:7]4[C:12](=[C:3]([F:2])[CH:4]=[CH:5][CH:6]=4)[O:11][CH2:10][CH2:9]3)[C:39]([N+:45]([O-:47])=[O:46])=[CH:40][N:41]=2)[CH:22]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 52911303(R)-8-fluorochroman-4-amine hydrochlorideHCID 59704889tert-Butyl 4-fluoro-2-(5-nitro-4-thiocyanatopyrimidin-2-ylamino)phenylcarbamate

생성물 1

HCID 66970500(R)-tert-Butyl 4-fluoro-2-(4-(8-fluorochroman-4-ylamino)-5-nitropyrimidin-2-ylamino)phenylcarbamate수율 83%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 6342Acetonitrile용매

실험 절차

A solution of the (R)-8-fluorochroman-4-amine hydrochloride (104 mg) in DMSO (2 mL) and potassium carbonate (141 mg) were added to a stirred solution of tert-butyl 4-fluoro-2-(5-nitro-4-thiocyanatopyrimidin-2-ylamino)phenylcarbamate (140 mg) in ACN (10 mL). The mixture was stirred for 15 hr at room temperature then partitioned between brine and EtOAc and separated. The aq. layer was washed with additional EtOAc, the combined organics were evaporated and purified via column chromatography, elution with 20-30% EtOAc/H gave the titled product in 83% yield. 1H-NMR (300 MHz, CDCl3) δ 9.1 (s, 1H), 8.7 (m, 1H), 8.2 (br s, 1H), 7.7 (m, 1H), 7.3 (m, 1H), 7.3-6.8 (m, 4H), 6.5 (s, 1H), 5.5 (br s, 1H), 4.4 (m 2H), 2.4 (m, 1H), 2.2 (m, 1H), 1.5 (s, 9H); MH+=515, 459 (-tBu).

후처리

  1. customthen partitioned between brine and EtOAc
  2. customseparated
  3. washThe aq. layer was washed with additional EtOAc
  4. customthe combined organics were evaporated
  5. custompurified via column chromatography, elution with 20-30% EtOAc/H

출처 및 근거

ORD 기록
ord-f6607f7f376146b69f700cdc31060f6f
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07884109B2

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