Ammonium Chloride → HCID 53353203, compound

HRID 2405112Notes

Reaction equation

HRID 2405112 reaction equation
[Si]([O:8][CH2:9][C:10]([C:13]1[CH:34]=[CH:33][C:16]([C:17]([NH:19][C:20]2[N:25]=[CH:24][C:23]3[C:26]([Cl:32])=[CH:27][N:28]([CH:29]4[CH2:31][CH2:30]4)[C:22]=3[CH:21]=2)=[O:18])=[CH:15][CH:14]=1)([CH3:12])[CH3:11])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].[NH4+].[Cl-]>C1COCC1>[Cl:32][C:26]1[C:23]2[CH:24]=[N:25][C:20]([NH:19][C:17](=[O:18])[C:16]3[CH:15]=[CH:14][C:13]([C:10]([CH3:12])([CH3:11])[CH2:9][OH:8])=[CH:34][CH:33]=3)=[CH:21][C:22]=2[N:28]([CH:29]2[CH2:31][CH2:30]2)[CH:27]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 67356328HCID 67356328, compound

Product 1

HCID 53353203HCID 53353203, compoundYield 84.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To 4-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-N-(3-chloro-1-cyclopropyl-1H-pyrrolo[3,2-c]pyridin-6-yl)benzamide (20 mg, 0.040 mmol) was added THF (800 μA). At room temperature, TBAF (1.0M solution in THF, 50 μl) was added. The mixture was heated to 60° C. for 1 hr. After reaction was completed, 2 ml saturated NH4Cl was added and the mixture was extracted with EtOAc (3×2 ml). Organic layers were combined, dried, filtered and concentrated. The crude product was purified by preparatory HPLC (TFA mode, 20-45% ACN in water). Product containing fractions were combined, and then extracted with EtOAc to remove residual TBAF to give the title compound as a white solid (13 mg, 84%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.98-1.05 (m, 1H) 1.05-1.12 (m, 1H) 1.26 (d, J=1.52 Hz, 7H) 3.44-3.55 (m, 3H) 4.77 (br. s., 1H) 7.50 (dd, J=8.59, 2.27 Hz, 2H) 7.62 (d, J=6.06 Hz, 1H) 7.96-8.05 (m, 2H) 8.34 (d, J=1.01 Hz, 1H) 8.51 (d, J=1.01 Hz, 1H) 8.61 (d, J=1.01 Hz, 1H) 8.57 (d, J=0.76 Hz, 1H) 10.64 (d, J=9.09 Hz, 1H); ESI-MS: m/z 384 (M+H)+.

Workup

  1. customAfter reaction
  2. extractionthe mixture was extracted with EtOAc (3×2 ml)
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by preparatory HPLC (TFA mode, 20-45% ACN in water)
  7. additionProduct containing fractions
  8. extractionextracted with EtOAc
  9. customto remove residual TBAF

Sources & evidence

ORD record
ord-daf39b55580e4db188075cc4b19ab45f
Source dataset
uspto-grants-2014_08
Patent number
US08802695B2

Reaction notes

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