Diisopropylcarbodiimide → HCID 11719945, compound

HRID 2102369Notes

Reaction equation

HRID 2102369 reaction equation
C(N=C=NC(C)C)(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:25]3[C:24]([O:26][CH2:27][CH2:28][CH2:29][O:30][C:31]4[CH:32]=[C:33]([CH:37]=[CH:38][CH:39]=4)[C:34](O)=[O:35])=[N:23][CH:22]=[N:21][C:20]=3[S:19][CH:18]=2)=[CH:13][CH:12]=1.Cl.[NH2:41][CH2:42][C:43]([NH2:45])=[O:44].ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C1C=CN=CC=1.CN(C)C=O>[NH2:45][C:43](=[O:44])[CH2:42][NH:41][C:34](=[O:35])[C:33]1[CH:37]=[CH:38][CH:39]=[C:31]([O:30][CH2:29][CH2:28][CH2:27][O:26][C:24]2[C:25]3[C:17]([C:14]4[CH:15]=[CH:16][C:11]([F:10])=[CH:12][CH:13]=4)=[CH:18][S:19][C:20]=3[N:21]=[CH:22][N:23]=2)[CH:32]=1

Participants

8

Reactant 5

HCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2723639Glycinamide hydrochlorideHCID 11611575HCID 11611575, compound

Product 1

HCID 11719945HCID 11719945, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

1,3-Diisopropylcarbodiimide (13.0 mg, 0.10 mmol) was added to a stirred mixture of 3-(3-{[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}propoxy)benzoic acid (21 mg, 0.050 mmol), 2-amino-acetamide hydrochloride (11 mg, 0.10 mmol), 1-hydroxybenzotriazole (6.7 mg, 0.05 mmol), diisopropylethylamine (40 mg, 0.30 mmol) and 4-dimethylaminopyridine (13 mg, 0.10 mmol) in N,N-dimethylformamide (1.0 mL). The mixture was stirred at room temperature for 6 hours and then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (30 mL), washed with aqueous sodium bicarbonate solution (2×25 mL) and the organic layer was separated and concentrated. The product was purified by column chromatography over silica gel using 5% methanol in 1:1 of ethyl acetate/hexanes to give 9.6 mg (40%) of N-(2-amino-2-oxoethyl)-3-(3-{[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy}propoxy)benzamide as a white solid. MS [M+H] 481.1, 1H NMR (CDCl3) δ (ppm) 8.68 (s, 1H), 7.60-7.24 (m, 4H), 7.21 (s, 1H), 7.18-6.95 (m, 3H), 6.90 (d, J=7.8 Hz, 1H), 6.31 (b, 1H), 5.62 (b, 1H), 4.59 (t, J=6.0 Hz, 2H), 4.19, (d, J=5.1 Hz, 2H), 3.74 (t, J=6.0 Hz, 2H), 2.10 (m, 2H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in ethyl acetate (30 mL)
  3. washwashed with aqueous sodium bicarbonate solution (2×25 mL)
  4. customthe organic layer was separated
  5. concentrationconcentrated
  6. customThe product was purified by column chromatography over silica gel using 5% methanol in 1:1 of ethyl acetate/hexanes

Sources & evidence

ORD record
ord-5c15d25bea9a48d3929fb35b2ebd0b84
Source dataset
uspto-grants-2009_08
Patent number
US07576080B2

Reaction notes

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