Propylamine → HCID 58728634, compound

HRID 1992095Notes

Reaction equation

HRID 1992095 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[S:11](Cl)(=[O:13])=[O:12].[CH2:15]([NH2:18])[CH2:16][CH3:17].C(N(CC)C(C)C)(C)C.Cl.Cl.[CH3:30][C:31]1[N:35]([CH:36]2[CH2:42][C@H:41]3[N:43]([CH2:44][CH2:45][C:46]4([C:52]5[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=5)[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]4)[C@H:38]([CH2:39][CH2:40]3)[CH2:37]2)[C:34]2[CH:58]=[CH:59][CH:60]=[CH:61][C:33]=2[N:32]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C)C=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:49]2[CH2:48][CH2:47][C:46]([CH2:45][CH2:44][N:43]3[C@H:41]4[CH2:40][CH2:39][C@@H:38]3[CH2:37][CH:36]([N:35]3[C:34]5[CH:58]=[CH:59][CH:60]=[CH:61][C:33]=5[N:32]=[C:31]3[CH3:30])[CH2:42]4)([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[CH2:51][CH2:50]2)=[O:8])=[CH:4][C:3]=1[S:11]([NH:18][CH2:15][CH2:16][CH3:17])(=[O:13])=[O:12]

Participants

8

Reactant 5

HCID 7852PropylamineHCID 756134-Chloro-3-(chlorosulphonyl)benzoic acidHCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68676313HCID 68676313, compound

Product 1

HCID 58728634HCID 58728634, compoundYield 43.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-chloro-3-(chlorosulfonyl)benzoic acid (25.4 mg, 0.1 mmol) in dichloromethane (3 mL) was added propylamine (9 μL, 0.11 mmol), N,N-diisopropylethylamine (39 mg, 0.3 mmol) and 4-N,N-dimethylaminopyridine (2 mg, 0.016 mmol). After the resultant mixture was stirred overnight, a solution of 2-methyl-1-{(1R,5S)-8-[2-(4-phenyl piperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole dihydrochloride (50 mg, 0.1 mmol) in N,N-dimethylforamide (3 mL) was added and followed by addition of N,N-diisopropylethylamine (39 mg, 0.3 mmol) and HATU (38 mg. 0.1 mmol). The reaction mixture was stirred for further 4 hours before it was quenched with saturated sodium bicarbonate solution and extracted with dichloromethane. The combined organic extracts were dried over anhydrous sodium sulfate. After evaporation of solvents, the residue was purified by flash chromatography, eluting with a gradient of 0-8% methanol in ethyl acetate to afford 2-chloro-5-[(4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]-N-propylbenzenesulfonamide as solid (30 mg, 43%). 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.65 (s, 2H), 7.38 (t, J=7.5 Hz, 2H), 7.30-7.23 (m, 4H), 7.19-7.12 (m, 2H), 5.10 (t, J=6.0 Hz, 1H), 4.64-4.59 (m, 1H), 4.19 (br, 1H), 3.48 (br, 1H), 3.34-3.35 (m, 4H), 2.90 (q, J=6.3 Hz, 2 H), 2.57 (s, 3H), 2.42-2.34 (m, 3H), 2.20 (br, 1H), 1.94-1.78 (m, 10H), 1.62 (d, J=6.4 Hz, 2H), 1.54-1.45 (m, 2H), 0.88 (t, J=7.5 Hz, 3H). HRMS m/z (M+H)+ calcd: 688.3088, obsd: 688.3063.

Workup

  1. customwas quenched with saturated sodium bicarbonate solution
  2. extractionextracted with dichloromethane
  3. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  4. customAfter evaporation of solvents
  5. customthe residue was purified by flash chromatography
  6. washeluting with a gradient of 0-8% methanol in ethyl acetate

Sources & evidence

ORD record
ord-fa3636f389864c779dbd6562e38b74b9
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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