Sodium Bicarbonate → tert-Butyl (4-(5-((S)-1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)cyclohex-3-en-1-yl)carbamate

HRID 2205629Notes

Reaction equation

HRID 2205629 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2Br)[CH3:10])[C:5]([C:22]#[N:23])=[C:4]([CH3:24])[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH2:38][CH2:37][CH:36]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:35][CH:34]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:16]=[C:15]3[CH:17]=[CH:18][N:19]([CH3:20])[C:14]3=[CH:13][C:12]=2[C:33]2[CH2:38][CH2:37][CH:36]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:44])([CH3:43])[CH3:45])[CH2:35][CH:34]=2)[CH3:10])[C:5]([C:22]#[N:23])=[C:4]([CH3:24])[N:3]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 66570714tert-butyl N-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl]carbamateHCID 118207725(S)-2-Amino-4-((1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-6-methylpyrimidine-5-carbonitrile

Product 1

HCID 118215172tert-Butyl (4-(5-((S)-1-((2-amino-5-cyano-6-methylpyrimidin-4-yl)amino)ethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)cyclohex-3-en-1-yl)carbamateYield 87%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with (S)-2-amino-4-((1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)-6-methylpyrimidine-5-carbonitrile (0.07 g, 0.181 mmol), tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl)carbamate (0.076 g, 0.236 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.015 g, 0.018 mmol) and sodium bicarbonate (0.030 g, 0.362 mmol) in dioxane (2 mL) and water (0.500 mL). The reaction mixture was heated to 100° C. for 40 minutes in a microwave reactor. Following reaction, the solvent was removed under a nitrogen stream and the residue was partitioned between ethyl acetate (20 mL) and water (20 mL). The organic phase was dried over anhydrous sodium sulfate and purified on a silica gel column (20-80% ethyl acetate/heptanes gradient) to give the title compound as a tan solid (79 mg, 87%). ESI-MS m/z [M+H]+ calc'd for C27H34N8O2, 503. found 503.

Workup

  1. customreaction
  2. customthe solvent was removed under a nitrogen stream
  3. customthe residue was partitioned between ethyl acetate (20 mL) and water (20 mL)
  4. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  5. custompurified on a silica gel column (20-80% ethyl acetate/heptanes gradient)

Sources & evidence

ORD record
ord-185936ee22064bb6ae52c5dfcb705ef0
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

Loading…