Diisopropylethylamine → 1-{5-tert-Butyl-2-[3-(tert-butyl-dimethyl-silanyloxy)-5-chloro-phenyl]-2H-pyrazol-3-yl}-3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

HRID 711183Notes

Reaction equation

HRID 711183 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:31])[NH:6][C:7]1[N:8]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[C:18]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH:17]=2)[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH3:34][N:35]1[CH2:39][CH2:38][CH2:37][C@H:36]1[C:40]1[N:44]2[CH:45]=[C:46]([O:49][C@H:50]3[C:59]4[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=4)[C@@H:53]([NH2:60])[CH2:52][CH2:51]3)[CH:47]=[CH:48][C:43]2=[N:42][N:41]=1.CCN(C(C)C)C(C)C>C1COCC1.O>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:60][C@@H:53]2[C:54]3[C:59](=[CH:58][CH:57]=[CH:56][CH:55]=3)[C@H:50]([O:49][C:46]3[CH:47]=[CH:48][C:43]4[N:44]([C:40]([C@@H:36]5[CH2:37][CH2:38][CH2:39][N:35]5[CH3:34])=[N:41][N:42]=4)[CH:45]=3)[CH2:51][CH2:52]2)=[O:31])[N:8]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[C:18]([O:23][Si:24]([C:27]([CH3:28])([CH3:30])[CH3:29])([CH3:25])[CH3:26])[CH:17]=2)[N:9]=1)([CH3:15])([CH3:14])[CH3:13]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 117666105(1S,4R)-4-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamineHCID 123756753{5-tert-Butyl-2-[3-(tert-butyl-dimethyl-silanyloxy)-5-chloro-phenyl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 1233369991-{5-tert-Butyl-2-[3-(tert-butyl-dimethyl-silanyloxy)-5-chloro-phenyl]-2H-pyrazol-3-yl}-3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaYield 107.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of Intermediate 62d (193 mg, 0.35 mmol) and Intermediate E (115 mg, 0.32 mmol) and DIPEA (166 μL, 0.94 mmol) in THF (3.5 mL) was stirred at reflux for 24 h. The cooled reaction mixture was diluted with water and extracted with DCM. The combined organics were dried and concentrated in vacuo to give the title compound (265 mg, 99%). LCMS (Method 3): Rt 3.82 min, m/z 769 [MH+].

Workup

  1. temperatureat reflux for 24 h
  2. customThe cooled reaction mixture
  3. extractionextracted with DCM
  4. customThe combined organics were dried
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ece698ad86034b68a130a2a987a80859
Source dataset
uspto-grants-2015_11
Patent number
US09181242B2

Reaction notes

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