Triethylamine → HCID 44600361, compound

HRID 882755Notes

Reaction equation

HRID 882755 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([OH:16])[CH2:13][CH:12]1[C:17]([OH:19])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[CH:22]1([N:26]2[CH2:32][CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH2:25][CH2:24][CH2:23]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(#N)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@@H:12]1[C:17]([N:29]1[CH2:30][CH2:31][CH2:32][N:26]([CH:22]2[CH2:23][CH2:24][CH2:25]2)[CH2:27][CH2:28]1)=[O:19])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1145371-[(Benzyloxy)carbonyl]-4-hydroxypyrrolidine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574239521-Cyclobutyl-1,4-diazepane dihydrochloride

Product 1

HCID 44600361HCID 44600361, compoundYield 45.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of cis-D-hydroxyproline (221.1 mg, 1.687 mmol) in CH2Cl2 (15 mL) was treated with diisopropylethylamine (0.60 mL) and chlorotrimethylsilane (0.60 mL). The mixture was stirred for 2 hours, cooled to 0° C. and treated with benzyl chloroformate (0.250 mL). The reaction was stirred for 15 h at rt and then extracted with 1 N NaOH/Et2O. The aqueous layer was acidified with 1 N HCl and extracted with EtOAc. The organic layer was dried and concentrated to give 4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester (0.270 g), which was used directly in the next step. A solution of 4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester (0.2377 g) in acetonitrile (20 mL) was treated with cyclobutyl-[1,4]diazepane dihydrochloride (0.2411 g), triethylamine (0.400 mL), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.4780 g). After 3 h, the reaction mixture was extracted with 1 N NaOH/CH2Cl2, and the organic layer was dried and concentrated. Purification by FCC provided the desired product (0.1628 g, 24% over two steps). MS (ESI): mass calcd. for C22H31N3O4, 401.50; m/z found, 402.3 [M+H]+.

Workup

  1. extractionthe reaction mixture was extracted with 1 N NaOH/CH2Cl2
  2. customthe organic layer was dried
  3. concentrationconcentrated
  4. customPurification by FCC

Sources & evidence

ORD record
ord-75341de140024c2393ec1c5e434347da
Source dataset
uspto-grants-2012_08
Patent number
US08236792B2

Reaction notes

Loading…