Hydrochloric Acid → N2-(3-chloro-4-(((3S,4S)-3-fluoropiperidin-4-yl)oxy)phenyl)-N4-((7R,8aS)-5,5-dimethyloctahydroindolizin-7-yl)-5-fluoropyrimidine-2,4-diamine

HRID 633423ノート

反応式

HRID 633423 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:17][C@H:16]3[N:12]([CH2:13][CH2:14][CH2:15]3)[C:11]([CH3:19])([CH3:18])[CH2:10]2)[C:5]([F:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:42]=[CH:41][C:25]([O:26][C@H:27]2[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][C@@H:28]2[F:40])=[C:24]([Cl:43])[CH:23]=1.CC1C=CC(S(O)(=O)=O)=CC=1.Cl>CC(O)C.O1CCOCC1>[Cl:43][C:24]1[CH:23]=[C:22]([NH:21][C:2]2[N:7]=[C:6]([NH:8][C@@H:9]3[CH2:17][C@H:16]4[N:12]([CH2:13][CH2:14][CH2:15]4)[C:11]([CH3:19])([CH3:18])[CH2:10]3)[C:5]([F:20])=[CH:4][N:3]=2)[CH:42]=[CH:41][C:25]=1[O:26][C@H:27]1[CH2:32][CH2:31][NH:30][CH2:29][C@@H:28]1[F:40]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acid2 回HCID 86704490(7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-5,5-dimethyloctahydroindolizin-7-amineHCID 86704517tert-butyl (3S,4S)-4-(4-amino-2-chlorophenoxy)-3-fluoropiperidine-1-carboxylate

生成物 1

HCID 86704518N2-(3-chloro-4-(((3S,4S)-3-fluoropiperidin-4-yl)oxy)phenyl)-N4-((7R,8aS)-5,5-dimethyloctahydroindolizin-7-yl)-5-fluoropyrimidine-2,4-diamine収率 50%

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of (7R,8aS)-N-(2-chloro-5-fluoropyrimidin-4-yl)-5,5-dimethyloctahydroindolizin-7-amine (0.2 g, 1.0 eq, 0.6 mmol), tert-butyl (3S,4S)-4-(4-amino-2-chlorophenoxy)-3-fluoropiperidine-1-carboxylate (0.2 g, 1.0 eq, 0.64 mmol) and PTSA (0.1 g, 0.9 eq, 0.6 mmol) was taken in iPrOH (10 mL) and heated at 100° C. for over night. After 18 hours of heating, reaction mixture was cooled to room temperature and PTSA (1.0 eq) was added to complete the deprotection of the Boc group. Then the reaction mixture was heated at 100° C. for 3 hours while stifling and cooled to room temperature. The volatiles were removed under vacuum to leave a crude solid. 4N HCl in dioxane (5 mL) was added to the crude mixture to ensure complete dprotection of the Boc group and the mixture was concentrated to dryness. Work-up and purification conditions used were the same as in Example 89 above for Compound 119, and gave the product as a solid in 50% yield.

後処理

  1. temperatureAfter 18 hours of heating
  2. customreaction mixture
  3. temperaturewas cooled to room temperature
  4. temperatureThen the reaction mixture was heated at 100° C. for 3 hours while stifling and
  5. temperaturecooled to room temperature
  6. customThe volatiles were removed under vacuum
  7. customto leave a crude solid
  8. concentrationthe mixture was concentrated to dryness
  9. custompurification conditions

出典と根拠

ORDレコード
ord-4b257267e2964b55891167106575c4b2
出典データセット
uspto-grants-2016_04
特許番号
US09321763B2

反応ノート

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