Methanol → 1-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-cyclohexyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

HRID 75624Notes

Reaction equation

HRID 75624 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:19])[NH:6][C:7]1[N:8]([CH2:16][CH2:17][OH:18])[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[CH:22]1([C:28]2[N:32]3[CH:33]=[C:34]([O:37][C@H:38]4[C:47]5[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=5)[C@@H:41]([NH2:48])[CH2:40][CH2:39]4)[CH:35]=[CH:36][C:31]3=[N:30][N:29]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.CCN(C(C)C)C(C)C.CO>O1CCOCC1.C(Cl)Cl>[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:48][C@@H:41]2[C:42]3[C:47](=[CH:46][CH:45]=[CH:44][CH:43]=3)[C@H:38]([O:37][C:34]3[CH:35]=[CH:36][C:31]4[N:32]([C:28]([CH:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[N:29][N:30]=4)[CH:33]=3)[CH2:39][CH2:40]2)=[O:19])[N:8]([CH2:16][CH2:17][OH:18])[N:9]=1)([CH3:13])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 86686717[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl esterHCID 86686729(1S,4R)-4-(3-Cyclohexyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Product 1

HCID 866867301-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-cyclohexyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-ureaYield 50.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A brown solution of Intermediate 26a (94.2 mg, 0.263 mmol), Intermediate 34c (90.6 mg, 0.250 mmol), and DIPEA (0.054 mL, 0.31 mmol) in dry dioxane (3 mL) was stirred at 75° C. for 16 h. The cooled solution was concentrated in vacuo, suspended in water (3 mL) and extracted with DCM (2×3 mL). The combined organics were passed through a hydrophobic frit and concentrated in vacuo to leave a dark brown oil. Flash chromatography (silica gel, 3-9% MeOH in DCM) gave a pale yellow solid. MDAP (Method 7) gave an off-white solid (72 mg, 50%). LCMS (Method 5): Rt 3.98 min, m/z 572.4 [MH+].

Workup

  1. concentrationThe cooled solution was concentrated in vacuo
  2. extractionextracted with DCM (2×3 mL)
  3. concentrationconcentrated in vacuo
  4. customto leave a dark brown oil

Sources & evidence

ORD record
ord-962f1e479b2047d58e5630a233b97cbe
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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