Water → HCID 71136775, compound

HRID 629917Notes

Reaction equation

HRID 629917 reaction equation
[N:1]([CH2:4][CH:5]1[CH:7]([CH3:8])[CH:6]1[C:9]1[N:14]=[C:13]2[N:15]([CH3:24])[C:16](=[O:23])[N:17]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:12]2=[CH:11][CH:10]=1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.[N-]=[N+]=[N-]>C1COCC1>[NH2:1][CH2:4][CH:5]1[CH:7]([CH3:8])[CH:6]1[C:9]1[N:14]=[C:13]2[N:15]([CH3:24])[C:16](=[O:23])[N:17]([CH2:18][C:19]([CH3:21])([CH3:20])[CH3:22])[C:12]2=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11776TriphenylphosphineHCID 33558AzideHCID 117702495HCID 117702495, compound

Product 1

HCID 71136775HCID 71136775, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

1-(2,2-Dimethylpropyl)-5-[2-(hydroxymethyl)-3-methylcyclopropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (35-1, 61.6 mg, 0.20 mmol, 1.0 equiv) was added to anhydrous DCM (2.0 mL) and cooled to −10° C. Triethylamine (54.9 μL, 0.42 mmol, 2.1 equiv) and methanesulfonyl chloride (17.4 μL, 0.22 mmol, 1.1 equiv) were added sequentially and the resulting reaction mixture was stirred for 1 min. Following this duration, TLC showed complete consumption of 35-1. The reaction mixture was partitioned between ethyl acetate (5 mL) and saturated NaHCO3 (5 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×5 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give a clear, yellow oil. The yellow oil (77 mg, 0.20 mmol, 1 equiv) and sodium azide (32.8 mg, 0.50 mmol, 2.5 equiv) were dissolved in DMF, cooled to 0° C. and added with sodium hydride (12.1 mg, 0.50 mmol, 2.5 equiv). The reaction mixture was stirred for 18 h. Following this duration, TLC showed complete consumption of the mesylate. Azide intermediate (5-(2-(azidomethyl)-3-methylcyclopropyl)-3-methyl-1-neopentyl-1H-imidazo[4,5-b]pyridin-2(3H)-one) was isolated by normal-phase HPLC (0-40% EtOAc:hexanes). 5-(2-(azidomethyl)-3-methylcyclopropyl)-3-methyl-1-neopentyl-1H-imidazo[4,5-b]pyridin-2(3H)-one (65 mg, 0.19 mmol, 1 equiv), triphenylphosphine (156 mg, 0.59 mmol, 3 equiv) and water (35.1 μL, 1.9 mmol, 9.8 equiv) were added with THF. The reaction mixture was stirred at 55° C. for 1 h. Following this duration, UPLC showed trace of the azide intermediate. Purification by reverse-phase HPLC (20-100% CH3CN:0.1% TFA in H2O) provided 35-2.

Workup

  1. customPurification by reverse-phase HPLC (20-100% CH3CN:0.1% TFA in H2O)
  2. customprovided 35-2

Sources & evidence

ORD record
ord-37af30a699cd4dd59c949bec61b844c6
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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