Hydrochloric Acid → 4-[(3-aminocyclobutyl)oxy]-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile

HRID 577678Notes

Reaction equation

HRID 577678 reaction equation
[C:1]([C:3]1[C:11]2[C:10]([O:12][CH:13]3[CH2:16][CH:15]([NH:17]C(=O)OC(C)(C)C)[CH2:14]3)=[N:9][C:8]([NH:25][C:26]3[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=3)=[N:7][C:6]=2[N:5]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[CH:4]=1)#[N:2].Cl>C(Cl)Cl>[NH2:17][CH:15]1[CH2:14][CH:13]([O:12][C:10]2[C:11]3[C:3]([C:1]#[N:2])=[CH:4][N:5]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:6]=3[N:7]=[C:8]([NH:25][C:26]3[CH:27]=[N:28][N:29]([CH3:31])[CH:30]=3)[N:9]=2)[CH2:16]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86679623tert-butyl {3-[(5-cyano-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]cyclobutyl}carbamate

Product 1

HCID 866796244-[(3-aminocyclobutyl)oxy]-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrileYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl {3-[(5-cyano-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]cyclobutyl}carbamate (cis:trans (1:1), 470 mg, 0.85 mmol) in DCM (20 mL) was added HCl (0.85 mL of 4 M in 1,4-dioxane, 3.4 mmol). After 20 hrs, the volatiles were removed and the reaction mixture was partitioned between DCM (50 mL) and saturated aqueous NaHCO3 (20 mL). The organic layer was separated, dried over Na2SO4 and evaporated to give the title compound (380 mg, 99% yield) as a 1:1 cis:trans isomeric mixture. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.41 (d, J=12.59 Hz, 1H) 8.10 (s, 1H) 7.96 (br. s., 1H) 7.55 (s, 1H) 5.53 (br. s., 2H) 3.82 (s, 3H) 3.61-3.73 (m, 1H) 3.52-3.60 (m, 4H) 3.04 (br. s., 1H) 2.71-2.85 (m, 1H) 2.15-2.40 (m, 2H) 1.76-1.92 (m, 1H) 0.76-0.91 (m, 1H) −0.12 (br. s., 9H). m/z (APCI+) for C21H30N8O2Si 455.1 (M+H)+.

Workup

  1. customthe volatiles were removed
  2. customthe reaction mixture was partitioned between DCM (50 mL) and saturated aqueous NaHCO3 (20 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. customevaporated

Sources & evidence

ORD record
ord-cb6dd79796d341109e1d60f3998dfe34
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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