Phosgene → HCID 57563066, compound

HRID 1726211Notes

Reaction equation

HRID 1726211 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=2)[CH:9]2[CH2:14][CH2:13][N:12]([CH:15]([CH3:29])[CH2:16][CH2:17][NH:18][C:19]([C:21]3[C:22]([CH3:28])=[N:23][CH:24]=[N:25][C:26]=3[CH3:27])=[O:20])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[C:39](Cl)(Cl)=[O:40].[Cl-].[NH4+].CC[N:47](C(C)C)C(C)C>C1(C)C=CC=CC=1>[C:37]([C:33]1[CH:32]=[C:31]([CH:36]=[CH:35][CH:34]=1)[CH2:30][N:8]([C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:39]([NH2:47])=[O:40])=[CH:7][CH:6]=1)[CH:9]1[CH2:14][CH2:13][N:12]([CH:15]([CH3:29])[CH2:16][CH2:17][NH:18][C:19]([C:21]2[C:26]([CH3:27])=[N:25][CH:24]=[N:23][C:22]=2[CH3:28])=[O:20])[CH2:11][CH2:10]1)#[N:38]

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 86602132HCID 86602132, compound

Product 1

HCID 57563066HCID 57563066, compoundYield 41.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 4,6-dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-amino-phenyl)-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (see EXAMPLE 154) (54 mg, 0.10 mmol) in toluene (1 mL) was added phosgene (20% in toluene, 82 μL, 0.15 mmol) and the resultant slurry was stirred at room temperature for 3.5 hours. The mixture was concentrated under reduced pressure and the residue was dissolved in DMF (1 mL). To the solution were added ammonium chloride (28 mg, 0.53 mmol) and DIPEA (110 μL, 0.64 mmol) and the mixture was stirred at room temperature for 25 hours. Standard work-up and purification afforded COMPOUND 159 as a white solid (23 mg, 39%). 1H NMR (CDCl3) δ0.90-1.10 (m, 5H), 1.54 (d, 1H, J=13.5 Hz), 1.74-1.83 (m, 3H), 2.17 (t, 1H, J=11.1 Hz), 2.50 (s, 6H), 2.56 (t, 1H, J=11.1 Hz), 2.73-2.84 (m, 3H), 3.31 (m, 1H), 3.56 (m, 1H), 3.82-3.89 (m, 1H), 3.89 (s, 2H), 4.72 (s, 2H), 6.51 (d, 2H, J=8.1 Hz), 6.58 (s, 1H), 7.05 (d, 2H, J=8.1 Hz), 7.41-7.56 (m, 4H), 8.62 (br s, 1H), 8.85 (s, 1H). 13C NMR (CDCl3) δ 13.44, 21.94, 29.21, 30.42, 30.73, 40.05, 43.58, 48.57, 51.99, 53.45, 56.55, 60.24, 112.55, 117.73, 118.98, 125.26, 128.41, 129.36, 129.93, 130.67, 130.88, 131.02, 141.60, 145.94, 157.52, 157.75, 163.11, 166.29. ES-MS m/z 555 (M+H). Anal. Calcd. for C31H38N8O2.0.8CH2Cl2: C, 61.34; H, 6.41; N, 18.00. Found. C, 61.52; H, 6.49; N, 17.93.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (1 mL)
  3. stirringthe mixture was stirred at room temperature for 25 hours
  4. customStandard work-up and purification

Sources & evidence

ORD record
ord-ab4d7c97054b40ba8fdd9c8676b59659
Source dataset
uspto-grants-2009_02
Patent number
US07491735B2

Reaction notes

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