Trimethylsilyl isocyanate → HCID 10121688, compound

HRID 970103Notes

Reaction equation

HRID 970103 reaction equation
C(N(C(C)C)CC)(C)C.C[Si]([N:14]=[C:15]=[O:16])(C)C.[OH:17][CH:18]([CH2:34][N:35]1[C:43]2[CH2:42][CH2:41][NH:40][CH2:39][C:38]=2[C:37]([C:44]2[CH:49]=[CH:48][C:47]([I:50])=[CH:46][CH:45]=2)=[N:36]1)[CH2:19][N:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=2[C:28]#[N:29])[CH2:22][CH2:21]1>CN(C1C=CN=CC=1)C.N1C=CC=CC=1.C(Cl)Cl>[C:28]([C:27]1[CH:30]=[CH:31][CH:32]=[CH:33][C:26]=1[N:23]1[CH2:22][CH2:21][N:20]([CH2:19][CH:18]([OH:17])[CH2:34][N:35]2[C:43]3[CH2:42][CH2:41][N:40]([C:15]([NH2:14])=[O:16])[CH2:39][C:38]=3[C:37]([C:44]3[CH:49]=[CH:48][C:47]([I:50])=[CH:46][CH:45]=3)=[N:36]2)[CH2:25][CH2:24]1)#[N:29]

Participants

7

Reactant 3

HCID 70696Trimethylsilyl isocyanateHCID 81531DiisopropylethylamineHCID 11342085HCID 11342085, compound

Product 1

HCID 10121688HCID 10121688, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Diisopropylethylamine (0.531 mL, 3.05 mmol), DMAP (5 mg), and trimethylsilyl isocyanate (0.413 mL, 3.05 mmol) were added to a solution of 2-(4-{2-hydroxy-3-[3-(4-iodo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-benzonitrile in pyridine (3 mL) and CH2Cl2 (6 mL). The reaction mixture was stirred for 20 h, then partitioned between aqueous NaHCO3 and CH2Cl2. The CH2Cl2 layer was washed with brine, dried (Na2SO4), and concentrated. The resulting product was dissolved in CH2Cl2 (5 mL) and treated with 21 wt % sodium ethoxide in EtOH (0.5 mL) for 3 h. The reaction mixture was washed with brine, dried (Na2SO4), and concentrated. Purification by column chromatography (silica, 0-10% MeOH/CH2Cl2) afforded 290 mg (78%) of the title compound. HPLC (reverse phase conditions), tR=4.21 min. MS (electrospray): m/z 612.2 (612.5, calculated for C27H30IN7O2, M++H). 1H NMR (400 MHz, CDCl3): 7.73 (d, J=8.6 Hz, 2H), 7.57 (dd, J=7.6, 1.6 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.36 (d, J=8.6 Hz, 2H), 7.05 (t, J=7.6 Hz, 1H), 7.00 (d, J=8.4 Hz, 1H), 4.64 (br s, 2H), 4.57 (br s, 2H), 4.30 (br s, 1H), 4.20 (dd, J=14.1, 3.3 Hz, 1H), 4.06 (dd, J=14.1, 6.3 Hz, 1H), 3.82-3.65 (m, 2H), 3.29-3.20 (m, 4H), 3.04-2.80 (m, 6H), 2.68 (br s, 2H).

Workup

  1. custompartitioned between aqueous NaHCO3 and CH2Cl2
  2. washThe CH2Cl2 layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. dissolutionThe resulting product was dissolved in CH2Cl2 (5 mL)
  6. additiontreated with 21 wt % sodium ethoxide in EtOH (0.5 mL) for 3 h
  7. washThe reaction mixture was washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification by column chromatography (silica, 0-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ff11bce1d7ed422fb963e3be08265595
Source dataset
uspto-grants-2007_12
Patent number
US07309703B2

Reaction notes

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