Hydrochloric Acid → 4-(6-(azetidin-3-ylmethyl)-2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)pyrido[3,2-d]pyrimidin-4-yl)morpholine

HRID 1043580Notes

Reaction equation

HRID 1043580 reaction equation
[CH:1]([C:4]1[N:8]([C:9]2[N:10]=[C:11]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[C:12]3[N:18]=[C:17]([CH2:19][CH:20]4[CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]4)[CH:16]=[CH:15][C:13]=3[N:14]=2)[C:7]2[CH:37]=[CH:38][CH:39]=[CH:40][C:6]=2[N:5]=1)([CH3:3])[CH3:2].Cl>O1CCOCC1>[NH:22]1[CH2:23][CH:20]([CH2:19][C:17]2[CH:16]=[CH:15][C:13]3[N:14]=[C:9]([N:8]4[C:7]5[CH:37]=[CH:38][CH:39]=[CH:40][C:6]=5[N:5]=[C:4]4[CH:1]([CH3:3])[CH3:2])[N:10]=[C:11]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[C:12]=3[N:18]=2)[CH2:21]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58404993tert-Butyl 3-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)azetidine-1-carboxylate

Product 1

HCID 673436554-(6-(azetidin-3-ylmethyl)-2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)pyrido[3,2-d]pyrimidin-4-yl)morpholine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 3-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)azetidine-1-carboxylate (0.2 g) was deprotected with 4N HCl in dioxane (0.9 mL) at room temperature over 1 hour. The reaction was concentrated to dryness to afford crude 4-(6-(azetidin-3-ylmethyl)-2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)pyrido[3,2-d]pyrimidin-4-yl)morpholine which was reacted with methyl 2-bromo-2-methylpropanoate (3 eq) and potassium carbonate (6 eq) at 75° C. for 3 hours. The reaction mixture loaded onto a Biotage isolute cartridge, eluted with 2M NH3 in MeOH then purified by reverse phase HPLC to yield 17.9 mg of 117. MS (Q1) 544.3 (M)+

Workup

  1. concentrationThe reaction was concentrated to dryness

Sources & evidence

ORD record
ord-63724810276740359bef26e017377cff
Source dataset
uspto-grants-2013_10
Patent number
US08563540B2

Reaction notes

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