Diisopropylcarbodiimide → HCID 71269800, compound

HRID 1429555Notes

Reaction equation

HRID 1429555 reaction equation
[CH3:1][C:2]([OH:40])([CH2:4][CH2:5][S:6]([N:9]1[CH2:14][CH2:13][C:12]([C:15]2[CH:39]=[CH:38][C:18]3[N:19]=[C:20]([O:22][CH:23]4[CH2:28][CH2:27][N:26]([C:29]5[N:34]=[CH:33][C:32]([CH2:35][CH2:36][CH3:37])=[CH:31][N:30]=5)[CH2:25][CH2:24]4)[S:21][C:17]=3[CH:16]=2)=[CH:11][CH2:10]1)(=[O:8])=[O:7])[CH3:3].[O:41]=[C:42]([O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])[CH2:43][CH2:44][C:45](O)=[O:46].N1(C2C=CN=CC=2)CCCC1.CC(C)N=C=NC(C)C>C(Cl)Cl>[C:45]([O:40][C:2]([CH3:3])([CH2:4][CH2:5][S:6]([N:9]1[CH2:14][CH2:13][C:12]([C:15]2[CH:39]=[CH:38][C:18]3[N:19]=[C:20]([O:22][CH:23]4[CH2:28][CH2:27][N:26]([C:29]5[N:30]=[CH:31][C:32]([CH2:35][CH2:36][CH3:37])=[CH:33][N:34]=5)[CH2:25][CH2:24]4)[S:21][C:17]=3[CH:16]=2)=[CH:11][CH2:10]1)(=[O:7])=[O:8])[CH3:1])(=[O:46])[CH2:44][CH2:43][C:42]([O:48][CH2:49][CH2:50][Si:51]([CH3:52])([CH3:54])[CH3:53])=[O:41]

Participants

6

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 755674-PyrrolidinopyridineHCID 11117509HCID 11117509, compound2×HCID 54596264HCID 54596264, compound

Product 1

HCID 71269800HCID 71269800, compoundYield 85.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-methyl-4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butan-2-ol (250 mg, 0.427 mmol), 4-oxo-4-(2-(trimethylsilyl)ethoxy)butanoic acid (compound 39B, 466 mg, 2.13 mmol), and 4-(pyrrolidin-1-yl)pyridine (95 mg, 0.640 mmol) in CH2Cl2 (8.6 mL) at rt was added DIC (332 μl 2.134 mmol). The mixture was heated to reflux for 5 h. The mixture was cooled to rt, diluted with CH2Cl2 (4 mL), and washed sequentially with cold aq. HCl (1 N, 3 mL), cold aq. NaHCO3 (10%, 2 mL), water (2 mL), and brine (2 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 45% EtOAc) to afford Compound 39B as a light yellow solid (287 mg, 85% yield). 1H NMR (500 MHz, CDCl3) δ 8.14 (s, 2H), 7.65-7.54 (m, 2H), 7.36 (dd, J=8.4, 1.9 Hz, 1H), 6.10-5.97 (m, 1H), 5.42 (tt, J=7.8, 3.8 Hz, 1H), 4.26-4.09 (m, 4H), 4.01 (d, J=3.0 Hz, 2H), 3.70-3.61 (m, 2H), 3.56 (t, J=5.6 Hz, 2H), 3.11-3.01 (m, 2H), 2.69-2.61 (m, 2H), 2.56-2.45 (m, 4H), 2.42-2.33 (m, 2H), 2.28-2.18 (m, 2H), 2.15 (m, 2H), 1.91 (dtd, J=12.4, 8.2, 3.9 Hz, 2H), 1.55 (dd, J=15.0, 7.4 Hz, 2H), 1.45 (s, 6H), 0.92 (dd, J=13.0, 5.7 Hz, 4H), 0.02 (m, 2H), 0.00 (s, 9H). LCMS (m/z)=787 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 5 h
  3. washwashed sequentially with cold aq. HCl (1 N, 3 mL), cold aq. NaHCO3 (10%, 2 mL), water (2 mL), and brine (2 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 45% EtOAc)

Sources & evidence

ORD record
ord-715fd47dd6f9416495729ed57f9b9a1c
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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