Methanesulfonyl chloride → Methanesulfonic acid 2-{3-[5-(3-{(1S,4R)-4-[3-(4-aza-spiro[2.5]oct-4-yl)-[1,2,4] triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-3-tert-butyl-pyrazol-1-yl]-phenoxy}-ethyl ester

HRID 630957Notes

Reaction equation

HRID 630957 reaction equation
[CH2:1]1[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]2[N:13]3[CH:14]=[C:15]([O:18][C@H:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[C@@H:22]([NH:29][C:30]([NH:32][C:33]5[N:34]([C:42]6[CH:47]=[CH:46][CH:45]=[C:44]([O:48][CH2:49][CH2:50][OH:51])[CH:43]=6)[N:35]=[C:36]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:37]=5)=[O:31])[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:2]1.CCN(C(C)C)C(C)C.[CH3:61][S:62](Cl)(=[O:64])=[O:63].C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[CH2:2]1[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][N:4]2[C:9]2[N:13]3[CH:14]=[C:15]([O:18][C@H:19]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[C@@H:22]([NH:29][C:30](=[O:31])[NH:32][C:33]5[N:34]([C:42]6[CH:43]=[C:44]([CH:45]=[CH:46][CH:47]=6)[O:48][CH2:49][CH2:50][O:51][S:62]([CH3:61])(=[O:64])=[O:63])[N:35]=[C:36]([C:38]([CH3:41])([CH3:39])[CH3:40])[CH:37]=5)[CH2:21][CH2:20]4)[CH:16]=[CH:17][C:12]3=[N:11][N:10]=2)[CH2:1]1

Participants

7

Reactant 4

HCID 31297Methanesulfonyl chloride2×HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 866872671-{(1S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-{5-tert-butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-urea

Product 1

HCID 86687268Methanesulfonic acid 2-{3-[5-(3-{(1S,4R)-4-[3-(4-aza-spiro[2.5]oct-4-yl)-[1,2,4] triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-3-tert-butyl-pyrazol-1-yl]-phenoxy}-ethyl esterYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A yellow-orange solution of Intermediate 148f (137 mg, 0.198 mmol), DIPEA (0.10 mL, 0.60 mmol) and methanesulfonyl chloride (45 mg, 0.40 mmol) in DCM (5 mL) was stirred at 0° C. for 30 min, and at RT for 30 min. DIPEA (0.052 mL, 0.30 mmol) and MsCl (23 mg, 0.20 mmol) were added and the solution stirred at RT for 30 min. Water (2 mL) and sat. aq. NaHCO3 solution (2 mL) were added and the mixture shaken. The aqueous was extracted with DCM (5 mL), then the combined organics passed through a hydrophobic frit and concentrated in vacuo to leave the title compound as a yellow solid (100%). LCMS (Method 3): Rt 3.80 min, m/z 769 [MH+].

Workup

  1. stirringthe mixture shaken
  2. extractionThe aqueous was extracted with DCM (5 mL)
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9def68377ad44ac2bdcb958bab3ea450
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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