3-Buten-1-ol → HCID 131730825, compound

HRID 1895774Notes

Reaction equation

[CH2:1]([O:5][C:6]([C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:46])[C@@H:15]([NH:31][C:32](=[O:45])[C@@H:33]([NH:37]C(OC(C)(C)C)=O)[CH:34]([CH3:36])[CH3:35])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH:18]=2)[NH:9]1)=[O:7])[CH2:2][CH:3]=[CH2:4].[CH2:47](OC([C@H]1NCCN(C(=O)[C@@H](NC(=O)[C@@H](NC(OC(C)(C)C)=O)C(C)C)CC2C=CC=C(O[Si](C(C)(C)C)(C)C)C=2)C1)=O)[CH2:48]/C=C/C=C.C(O)CC=C>>[CH2:1]([O:5][C:6]([C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:46])[C@@H:15]([NH:31][C:32](=[O:45])[C@@H:33]([NH2:37])[CH:34]([CH3:36])[CH3:35])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][Si:24]([C:27]([CH3:28])([CH3:30])[CH3:29])([CH3:25])[CH3:26])[CH:18]=2)[NH:9]1)=[O:7])[CH2:2]/[CH:3]=[CH:4]/[CH:47]=[CH2:48]

Participants

Reactant 3

HCID 693893-Buten-1-ol

HCID 67957724HCID 67957724, compound2×

HCID 88532155HCID 88532155, compound

Product 1

HCID 131730825HCID 131730825, compound

Procedure

A solution of 10d (83.5 mg, 0.485 mmol.) in anhydrous dimethylformamide (4 ml) was cooled to 0° C. before adding N,N-diisopropylethylamine (340 uL, 1.94 mmol.) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (185 mg, 0.485 mmol.) The reaction mixture was stirred at 0° C. for 20 minutes before addition of (S)-1-{(S)-2-((S)-2-amino-3-methylbutyryl amino)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (E)-hexa-3,5-dienyl ester (285 mg, 0.485 mmol.)* in anhydrous dimethylformamide (4 ml). The reaction mixture was stirred at room temperature for 15 hours. The reaction mixture was the diluted with pH7 phosphate buffer (0.5M, 20 ml) then extracted with ethyl acetate (3×20 ml). The combined extract was washed with brine (3×20 ml), dried over sodium sulfate, filtered and evaporated to give a brown gum. The gum was purified on a silica column eluting with 60% ethyl acetate, 40% hexane to yield 11a as a colourless solid (133 mg, 37%). 1H NMR δ (300 MHz NMR, CDCl3) 0.17-0.21 (s, 6H), 0.87-0.96 (m, 6H) 0.96-1.01 (s, 9H), 1.14-1.20 (d, 3H, J=7.1 Hz), 1.35-1.85 (m, 7H), 2.08-2.21 (m, 3H), 2.39-2.53 (m, 3H), 2.65-3.01 (m, 3H), 3.31-3.45 (m, 4H), 3.50-3.57 (d, 1H, J=11.2), 4.09-4.35 (m, 5H), 4.93-5.20 (m, 3H), 5.57-5.90 (m, 3H), 6.08-6.19 (m, 1H), 6.25-6.40 (m, 1H), 6.45-6.59 (m, 2H), 6.64-6.75 (m, 2H), 6.78-6.85 (d, 1H, J=7.8 Hz), 7.07-7.15 (t, 1H, J=7.8 Hz). LCMS (m/z) 741.44 [M+H] Tr=5.72 min. (S)-1-{(S)-2-((S)-2-amino-3-methylbutyryl amino)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (E)-hexa-3,5-dienyl ester was prepared from the corresponding BOC protected product ((S)-((E)-hexa-3,5-dienyl)1-((S)-2-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanamido)-3-(3-(tert-butyldimethylsilyloxy)phenyl)propanoyl)piperazine-3-carboxylate) in a similar manner to that described for the preparation of 3b from 3a. In turn, (S)-((E)-hexa-3,5-dienyl)1-((S)-2-((S)-2-(tert-butoxycarbonylamino)-3-methylbutanamido)-3-(3-(tert-butyldimethylsilyloxy)phenyl)propanoyl)piperazine-3-carboxylate was prepared as described in the synthesis of 3a except substituting (E)-hexa-3,5-dien-1-ol for but-3-en-1-ol.

Sources & evidence

ORD record: ord-2c5eedc198c249caa4622e4bb78edd69
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513184B2

Reaction notes

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