Ammonia → 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-3-triisopropylsilanyloxy-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

HRID 2284965Notes

Reaction equation

HRID 2284965 reaction equation
[CH:1]([Si:4]([CH:35]([CH3:37])[CH3:36])([CH:32]([CH3:34])[CH3:33])[O:5][C@H:6]1[CH2:10][CH2:9][N:8]([C:11]2[N:15]3[CH:16]=[C:17]([O:20][C@H:21]4[C:30]5[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=5)[C@@H:24]([NH2:31])[CH2:23][CH2:22]4)[CH:18]=[CH:19][C:14]3=[N:13][N:12]=2)[CH2:7]1)([CH3:3])[CH3:2].ClC(Cl)(Cl)C[O:41][C:42](=O)[NH:43][C:44]1[N:45]([C:53]2[CH:58]=[CH:57][C:56]([CH3:59])=[CH:55][CH:54]=2)[N:46]=[C:47]([C:49]([CH3:52])([CH3:51])[CH3:50])[CH:48]=1.CCN(C(C)C)C(C)C.N>CN(C=O)C.CO.C(Cl)Cl>[C:49]([C:47]1[CH:48]=[C:44]([NH:43][C:42]([NH:31][C@@H:24]2[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C@H:21]([O:20][C:17]3[CH:18]=[CH:19][C:14]4[N:15]([C:11]([N:8]5[CH2:9][CH2:10][C@H:6]([O:5][Si:4]([CH:1]([CH3:3])[CH3:2])([CH:32]([CH3:34])[CH3:33])[CH:35]([CH3:37])[CH3:36])[CH2:7]5)=[N:12][N:13]=4)[CH:16]=3)[CH2:22][CH2:23]2)=[O:41])[N:45]([C:53]2[CH:58]=[CH:57][C:56]([CH3:59])=[CH:55][CH:54]=2)[N:46]=1)([CH3:52])([CH3:50])[CH3:51]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 86686994(1S,4R)-4-[3-((S)-3-Triisopropylsilanyloxy-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

Product 1

HCID 866869951-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-3-triisopropylsilanyloxy-pyrrolidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureaYield 23%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of Intermediate 26c (70 mg, 0.134 mmol), (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (Synthetic Communications, 2009, 39, 3999-4009, which is incorporated herein by reference in its entirety; 81 mg, 0.201 mmol) and DIPEA (70 mg, 0.54 mmol) in DMF (2 mL) was stirred at 60° C. for 30 min. The reaction mixture was applied to an SCX-2 cartridge (5 g) and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave a residue. FCC, using 0-10% [2M NH3 in MeOH] in DCM, gave the title compound as an off-white foam (19 mg, 23%). LCMS (Method 1): Rt 4.70, m/z 777 [MH+].

Workup

  1. washwashed with MeOH
  2. washThe product was eluted with 2M NH3 in MeOH
  3. concentrationconcentration in vacuo
  4. customgave a residue

Sources & evidence

ORD record
ord-0712efffc6554a3f9379fb4a11ba3aa4
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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