4-Methylmorpholine → HCID 86708118、化合物

HRID 1497817ノート

反応式

HRID 1497817 の反応式
[C:1]([O:5][C:6]([N:8]([CH3:15])[CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:31][C:32]1[N:64]=[C:35]2[C:36]([C:54]3[CH:59]=[CH:58][CH:57]=[C:56]([C:60]([F:63])([F:62])[F:61])[CH:55]=3)=[C:37]([CH3:53])[C:38]([C:40]3[N:44]([C:45]4[CH:52]=[CH:51][C:48]([C:49]#[N:50])=[CH:47][CH:46]=4)[N:43]=[CH:42][CH:41]=3)=[CH:39][N:34]2[N:33]=1.C(OC(N(C)CCCC(OC(OCC(C)C)=O)=O)=O)(C)(C)C>C1COCC1>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][CH2:11][C:12](=[O:14])[NH:31][C:32]1[N:64]=[C:35]2[C:36]([C:54]3[CH:59]=[CH:58][CH:57]=[C:56]([C:60]([F:62])([F:63])[F:61])[CH:55]=3)=[C:37]([CH3:53])[C:38]([C:40]3[N:44]([C:45]4[CH:52]=[CH:51][C:48]([C:49]#[N:50])=[CH:47][CH:46]=4)[N:43]=[CH:42][CH:41]=3)=[CH:39][N:34]2[N:33]=1)[CH3:15])([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 5

HCID 79724-Methylmorpholine3 回HCID 62365Isobutyl chloroformate3 回HCID 106563904-{[(Tert-butoxy)carbonyl](methyl)amino}butanoic acid3 回HCID 730509764-{5-[2-Amino-7-methyl-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-pyrazol-1-yl}-benzonitrileHCID 86708119HCID 86708119、化合物2 回

生成物 1

HCID 86708118HCID 86708118、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒4 回

反応条件

温度
-22 °C

実験手順

A solution of 4-(tert-butoxycarbonyl-methyl-amino)-butyric acid (109 mg, 0.50 mmol) in THF (5 mL) was treated with 4-methyl-morpholine (101 mg, 1.0 mmol) followed by isobutyl chloroformate (68 mg, 0.5 mmol) and cooled to −22° C. under argon. The reaction mixture was stirred for 20 mins while warming to −15° C. After re-cooling to −24° C., 4-{5-[2-amino-7-methyl-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]-pyrazol-1-yl}-benzonitrile (Ex. 1, 230 mg, 0.50 mmol) was added and the resulting suspension was slowly warmed to RT and stirred for 16 hrs. The reaction mixture was treated with a fresh batch of 1-({[(4-{[(tert-butoxy)carbonyl] (methyl)-amino}butanoyl)oxy]carbonyl}oxy)-2-methylpropane prepared from a solution of 4-(tert-butoxycarbonyl-methyl-amino)-butyric acid (218 mg, 1.0 mmol) in THF (5 mL), 4-methyl-morpholine (101 mg, 1.0 mmol) and isobutyl chloroformate (137 mg, 1.0 mmol) at RT. The reaction mixture was stirred at RT for 24 hrs and then heated at 60° C. for 7 hrs. After standing at RT for 18 hrs, the volatiles were removed in vacuo and the resulting residue was purified by flash chromatography eluting with a gradient of 0-100% EtOAc in DCM. The product containing fractions were concentrated in vacuo and the resulting residue (456 mg, 0.5 mmol) in THF (5 mL) was treated with a fresh batch of 1-({[(4-{[(tert-butoxy)carbonyl] (methyl)amino}butanoyl)oxy]carbonyl}oxy)-2-methylpropane prepared from a solution of 4-(tert-butoxycarbonyl-methyl-amino)-butyric acid (1.09 g, 5.0 mmol) in THF (20 mL), 4-methyl-morpholine (760 mg, 7.55 mmol) and isobutyl chloroformate (680 mg, 5.01 mmol) at RT. The resulting mixture was heated at 50° C. for 65 hrs and then purified by flash chromatography eluting with a gradient of 0-100% EtOAc in DCM followed by 10% MeOH in DCM affording the title compound (241 mg).

後処理

  1. temperaturewhile warming to −15° C
  2. temperatureAfter re-cooling to −24° C.
  3. temperaturethe resulting suspension was slowly warmed to RT
  4. stirringstirred for 16 hrs
  5. stirringThe reaction mixture was stirred at RT for 24 hrs
  6. temperatureheated at 60° C. for 7 hrs
  7. waitAfter standing at RT for 18 hrs
  8. customthe volatiles were removed in vacuo
  9. customthe resulting residue was purified by flash chromatography
  10. washeluting with a gradient of 0-100% EtOAc in DCM
  11. additionThe product containing fractions
  12. concentrationwere concentrated in vacuo
  13. temperatureThe resulting mixture was heated at 50° C. for 65 hrs
  14. custompurified by flash chromatography
  15. washeluting with a gradient of 0-100% EtOAc in DCM

出典と根拠

ORDレコード
ord-6efe8fab5bb945318ea3c4bb9195f615
出典データセット
uspto-grants-2015_12
特許番号
US09199984B2

反応ノート

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