Morpholine → (R)-morpholino(2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-yl)methanone

HRID 1692013Notes

Reaction equation

HRID 1692013 reaction equation
[N:1]1([C@@H:7]2[CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]4[CH:20]=[C:19]([C:21]([OH:23])=O)[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[O:27]1[CH2:28][CH2:29][N:24]([C:21]([C:19]2[CH:18]=[CH:17][C:15]3[N:16]=[C:12]([N:9]4[CH2:10][CH2:11][C@@H:7]([N:1]5[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]5)[CH2:8]4)[S:13][C:14]=3[CH:20]=2)=[O:23])[CH2:25][CH2:26]1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44124707(R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole-6-carboxylic acid

Product 1

HCID 44124708(R)-morpholino(2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-yl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole-6-carboxylic acid, the product of Example 54 (40 mg, 0.121 mmol), morpholine (12 μL, 0.133 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (51 mg, 0.133 mmol) were combined in dichloromethane (2 mL). Triethyl amine (52 μL, 0.374 mmol) was added and mixture was stirred overnight at room temperature. The mixture was diluted with dichloromethane and washed with a 1 N aqueous sodium hydroxide solution. The organic layer was absorbed on silica gel and the mixture was purified by column chromatography eluting with a gradient of methanol and dichloromethane (2-18%) to afford the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.41-1.54 (m, 2 H) 1.59-1.70 (m, 4 H) 1.94-2.12 (m, 1 H) 2.24-2.38 (m, 1 H) 2.39-2.60 (m, 4 H) 2.95-3.11 (m, 1 H) 3.37-3.48 (m, 1 H) 3.49-3.61 (m, 1 H) 3.61-3.80 (m, 9 H) 3.81-3.93 (m, 1 H) 7.33 (dd, J=8.31, 1.87 Hz, 1 H) 7.55 (d, J=8.14 Hz, 1 H) 7.73 (d, J=1.70 Hz, 1 H); MS (ESI+) m/z 401.1 (M+H)+.

Workup

  1. washwashed with a 1 N aqueous sodium hydroxide solution
  2. customThe organic layer was absorbed on silica gel
  3. customthe mixture was purified by column chromatography
  4. washeluting with a gradient of methanol and dichloromethane (2-18%)

Sources & evidence

ORD record
ord-2a0bb307514344babedee86ffb8d65d0
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

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