Hydrochloric Acid → HCID 178457041, compound

HRID 511628Notes

Reaction equation

HRID 511628 reaction equation
Cl.[Cl:2][C:3]1[C:4]([C:51]([F:54])([F:53])[F:52])=[CH:5][C:6]2[N:10]=[C:9]([CH2:11][CH:12]3[CH2:15][CH:14]([CH2:16][N:17]([CH2:21][C@@H:22]4[C@H:26]5[O:27]C(C)(C)[O:29][C@H:25]5[C@H:24]([N:32]5[C:36]6[N:37]=[CH:38][N:39]=[C:40]([NH2:41])[C:35]=6[CH:34]=[CH:33]5)[CH2:23]4)[CH:18]([CH3:20])[CH3:19])[CH2:13]3)[N:8](COCC[Si](C)(C)C)[C:7]=2[CH:50]=1>CO>[NH2:41][C:40]1[C:35]2[CH:34]=[CH:33][N:32]([C@@H:24]3[CH2:23][C@H:22]([CH2:21][N:17]([CH2:16][CH:14]4[CH2:15][CH:12]([CH2:11][C:9]5[NH:8][C:7]6[CH:50]=[C:3]([Cl:2])[C:4]([C:51]([F:53])([F:52])[F:54])=[CH:5][C:6]=6[N:10]=5)[CH2:13]4)[CH:18]([CH3:20])[CH3:19])[C@@H:26]([OH:27])[C@H:25]3[OH:29])[C:36]=2[N:37]=[CH:38][N:39]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 677763577-[(3aS,4R,6R,6aR)-6-({[(3-{[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutyl)methyl](propan-2-yl)amino]methyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Product 1

HCID 178457041HCID 178457041, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

12N HCl (1.5 ml) was added slowly to a solution of 7-[(3aS,4R,6R,6aR)-6-({[(3-{[6-chloro-5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutyl)methyl](propan-2-yl)amino]methyl)-2,2-dimethyl-hexahydrocyclopenta[d][1,3]dioxol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (174 mg, 0.22 mmol) in MeOH (1.5 ml) and stirred at 40° C. for 6 h. The reaction was monitored by LCMS, no starting material seen after 2.5 h. The reaction mixture was concentrated in vacuo, then basified with 7N NH3 in MeOH (5 ml). This was then evaporated to dryness. Purification by silica gel column chromatography, eluting with 7N NH3 in MeOH:DCM (1:9) gave the desired product (36 mg, 27%) as a white solid; MS (ESI+) for C29H35ClF3N7O2 m/z 606.30 [M+H]+; HPLC purity 100% (ret. time, 2.59 min); 1H NMR (500 MHz, MeOD) δH ppm 0.93-1.09 (6H, m), 1.41-1.64 (2H, m), 1.76-2.06 (1H, m), 2.15-2.65 (9H, m), 2.65-2.88 (1H, m), 2.91-3.13 (3H, m), 3.80-4.09 (1H, m), 4.19-4.46 (1H, m), 4.88-4.94 (1H, m), 6.46-6.77 (1H, m), 7.19 (1H, d, J=3.63 Hz), 7.69 (1H, s), 7.89 (1H, s), 8.06 (1H, s)

Workup

  1. waitno starting material seen after 2.5 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customThis was then evaporated to dryness
  4. customPurification by silica gel column chromatography
  5. washeluting with 7N NH3 in MeOH:DCM (1:9)

Sources & evidence

ORD record
ord-fa059c69b8394fcb86af2b283162943c
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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