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

HRID 1363170ノート

反応式

HRID 1363170 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 6342Acetonitrile溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f6607f7f376146b69f700cdc31060f6f
出典データセット
uspto-grants-2011_02
特許番号
US07884109B2

反応ノート

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