Diisopropylcarbodiimide → HCID 57988818, compound

HRID 1668306Notes

Reaction equation

HRID 1668306 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:16][C:15]3[C:14](=[O:17])[N:13]([C:18]4[CH:23]=[CH:22][C:21]([O:24][CH2:25][C@@H:26]([CH:28]5[CH2:30][CH2:29]5)[OH:27])=[C:20]([O:31][CH3:32])[CH:19]=4)[CH:12]=[N:11][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.C(N=C=NC(C)C)(C)C.C(OC([NH:49][C@H:50]([C:54](O)=[O:55])[CH:51]([CH3:53])[CH3:52])=O)(C)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[NH2:49][C@@H:50]([CH:51]([CH3:53])[CH3:52])[C:54]([O:27][C@H:26]([CH:28]1[CH2:29][CH2:30]1)[CH2:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([N:13]2[C:14](=[O:17])[C:15]3[S:16][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)=[CH:9][C:10]=3[N:11]=[CH:12]2)=[CH:19][C:20]=1[O:31][CH3:32])=[O:55]

Participants

6

Reactant 3

HCID 12734DiisopropylcarbodiimideHCID 83693Boc-L-ValineHCID 444764516-(4-Chlorophenyl)-3-{4-[(2R)-2-cyclopropyl-2-hydroxyethoxy]-3-methoxyphenyl}thieno[3,2-d]pyrimidin-4(3H)-one

Product 1

HCID 57988818HCID 57988818, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of (R)-6-(4-chlorophenyl)-3-(4-(2-cyclopropyl-2-hydroxyethoxy)-3-methoxyphenyl)-thieno[3,2-d]pyrimidin-4(3H)-one described in Example 1 (1.3 g, 2.33 mmol), diisopropylcarbodiimide (0.88 g, 6.99 mmol), 4-dimethylaminopyridine (142 mg, 1.16 mmol) and N-(t-butoxycarbonyl)-L-valine (1.52 g, 6.99 mmol) in CH2Cl2 (10 mL) was stirred at rt for 19 h. By LCMS analysis no starting alcohol remained. The suspension was diluted with CH2Cl2 and washed with aq NaHCO3. After extracting the aqueous layer with CH2Cl2, the combined organic layers were washed sequentially with water and brine, dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, EtOAC/hexane 0 to 40% gradient) to afford the title compound (1.12 g) as a white solid. 1H NMR (CDCl3) δ 0.41-0.46 (m, 1H), 0.49-0.53 (m, 1H), 0.58-0.63 (m, 1H), 0.64-0.68 (m, 1H), 0.925 (d, J=7 Hz), 3H), 0.99 (d, J=7 Hz), 1.16-1.19 (m, 1H), 1.44 (s, 9H), 2.19-2.23 (m, 1H), 3.86 (s, 3H), 4.23-4.32 (m, 3H), 4.67-4.71 (m, 1H), 5.06 (d, J=2 Hz, 1H), 6.92-6.95 (m, 2H), 7.04 (d, J=2 Hz, 1H), 7.26 (s, 2H), 7.45 (d, J=2 Hz), 7.54 (s, 1H), 7.66 (d, J=2 Hz, 2H), 8.16 (s, 1H). LCMS (ES): m/z 669 [M+H].

Workup

  1. washwashed with aq NaHCO3
  2. extractionAfter extracting the aqueous layer with CH2Cl2
  3. washthe combined organic layers were washed sequentially with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (silica gel, EtOAC/hexane 0 to 40% gradient)

Sources & evidence

ORD record
ord-caee4a52ea1d4c17afee12f94fe9ef54
Source dataset
uspto-grants-2011_08
Patent number
US07989433B2

Reaction notes

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