Diisopropylethylamine → N-(5-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-7-fluoro-1H-pyrrolo[3,2-c]pyridine-3-carbonyl}-pyridin-3-yl)-2-(3-cyclopropyl-pyrazol-1-yl)-acetamide

HRID 1753025Notes

Reaction equation

HRID 1753025 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:14]3[CH:15]=[N:16][CH:17]=[C:18]([F:19])[C:13]=3[N:12]([C:20]([CH3:31])([CH3:30])[CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[CH:32]1([C:35]2[CH:39]=[CH:38][N:37]([CH2:40][C:41](O)=[O:42])[N:36]=2)[CH2:34][CH2:33]1.CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C1COCC1>[C:26]([Si:23]([CH3:24])([CH3:25])[O:22][CH2:21][C:20]([N:12]1[C:13]2[C:18]([F:19])=[CH:17][N:16]=[CH:15][C:14]=2[C:10]([C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:41](=[O:42])[CH2:40][N:37]3[CH:38]=[CH:39][C:35]([CH:32]4[CH2:33][CH2:34]4)=[N:36]3)[CH:7]=[N:6][CH:5]=2)=[O:9])=[CH:11]1)([CH3:31])[CH3:30])([CH3:29])([CH3:28])[CH3:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 64853962-(3-cyclopropyl-1H-pyrazol-1-yl)acetic acidHCID 90092825HCID 90092825, compound

Product 1

HCID 90093921N-(5-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-7-fluoro-1H-pyrrolo[3,2-c]pyridine-3-carbonyl}-pyridin-3-yl)-2-(3-cyclopropyl-pyrazol-1-yl)-acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of (5-amino-pyridin-3-yl)-{1-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-7-fluoro-1H-pyrrolo[3,2-c]pyridin-3-yl}-methanone (Preparation 29, 35 mg, 79 μmol), (3-cyclopropyl-pyrazol-1-yl)-acetic acid (17.74 mg, 106 μmol) and DIPEA (48.97 μL, 277 μmol) in THF (3 mL), T3P (166 μL, 277 μmol) was added and the mixture stirred at 25° C. for 18 hours. The reaction was evaporated under reduced pressure, the residue partitioned between water and ethyl acetate, the organic extracts washed with saturated sodium bicarbonate solution, dried over sodium sulphate, evaporated in vacuo and triturated with pentane-ether to afford the title compound as an off white solid (91%, 42 mg) that was taken directly on to the next step.

Workup

  1. customThe reaction was evaporated under reduced pressure
  2. customthe residue partitioned between water and ethyl acetate
  3. washthe organic extracts washed with saturated sodium bicarbonate solution
  4. dry with materialdried over sodium sulphate
  5. customevaporated in vacuo
  6. customtriturated with pentane-ether

Sources & evidence

ORD record
ord-41200e73705c4528a7ad0842368089ba
Source dataset
uspto-grants-2015_10
Patent number
US09163021B2

Reaction notes

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