Morpholine → HCID 89922660, 화합물

HRID 921926노트

반응식

HRID 921926 반응식
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][C:10](=O)[CH3:11])[C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([N:22]([CH:32]2[CH2:34][CH2:33]2)CC2C=CC(OC)=CC=2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1.C(OC)(OC)OC.C([BH3-])#N.[Na+]>C1COCC1.CO.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH:10]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[CH3:11])[C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([NH:22][CH:32]2[CH2:34][CH2:33]2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1

참가 물질

8

반응물 4

HCID 8083MorpholineHCID 9005Trimethyl orthoformateHCID 5003444Sodium cyanoborohydrideHCID 89922506HCID 89922506, 화합물

생성물 1

HCID 89922660HCID 89922660, 화합물수율 42.9%

시약·촉매·용매 3

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

2-((2-chloro-5-cyano-4-(3-oxobutyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (38 mg, 0.070 mmol) and morpholine (9.2 mg, 0.10 mmol) was taken up in THF (0.2 mL) and MeOH (0.2 mL). Trimethyl orthoformate (0.078 mL, 0.070 mmol) and sodium cyanoborohydride (8.8 mg, 0.14 mmol) was then added. The reaction was stirred at room temperature overnight. The reaction was diluted with EtOAc and washed with aq. NaHCO3, then brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was taken up in DCM (0.25 mL) and anisole (0.025 mL) was added, followed by TFA (0.25 mL). The reaction was stirred at room temperature overnight. The reaction was then concentrated in vacuo and purified by preparative HPLC to provide 2-((2-chloro-5-cyano-4-(3-morpholinobutyl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (15.3 mg, 0.030 mmol, 42.5% yield).

후처리

  1. washwashed with aq. NaHCO3
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionanisole (0.025 mL) was added
  6. stirringThe reaction was stirred at room temperature overnight
  7. concentrationThe reaction was then concentrated in vacuo
  8. custompurified by preparative HPLC

출처 및 근거

ORD 기록
ord-d85d5508643049b4b9fb2602f9b8b9ed
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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