Methyl bromoacetate → (+/-)-(2-{1-[(3-tert-Butoxycarbonylaminopropyl)-(4-methylbenzoyl)-amino]-propyl}-4-oxo-4H-pyrrolo[2,1-f][1,2,4]triazin-3-yl)-acetic acid methyl ester

HRID 1795939Notes

Reaction equation

[C:1]([O:5][C:6](=[O:34])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1)[CH:12]([C:15]1[NH:20][C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][N:17]2[N:16]=1)[CH2:13][CH3:14])([CH3:4])([CH3:3])[CH3:2].C(OC(=O)NCCCN(C(C1N(CC2C=CC(F)=CC=2)C(=O)C2=CC=CN2N=1)CC)C(=O)C1C=CC(C)=CC=1)(C)(C)C.Br[CH2:78][C:79]([O:81][CH3:82])=[O:80]>>[CH3:82][O:81][C:79](=[O:80])[CH2:78][N:20]1[C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][N:17]2[N:16]=[C:15]1[CH:12]([N:11]([CH2:10][CH2:9][CH2:8][NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:34])[C:25](=[O:33])[C:26]1[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=1)[CH2:13][CH3:14]

Participants

Reactant 3

HCID 60984Methyl bromoacetate

HCID 69591796HCID 69591796, compound

HCID 136411691(+/-)-(3-{(4-Methylbenzoyl)-[1-(4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4] triazin-2-yl)-propyl]amino}propyl)carbamic acid tert-butyl ester

Product 1

HCID 69591790(+/-)-(2-{1-[(3-tert-Butoxycarbonylaminopropyl)-(4-methylbenzoyl)-amino]-propyl}-4-oxo-4H-pyrrolo[2,1-f][1,2,4]triazin-3-yl)-acetic acid methyl esterYield 31%

Procedure

(±)-(3-{(4-Methylbenzoyl)-[1-(4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4] triazin-2-yl)-propyl]amino}propyl)carbamic acid tert-butyl ester (Example 3 A, 100 mg, 0.21 mmol) was converted to the title compound (35 mg, 31%) in a manner similar to the preparation of (±)-{3-[{1-[3-(4-fluorobenzyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl]-propyl}-(4-methylbenzoyl)-amino]-propyl}-carbamic acid tert-butyl ester, except that methyl bromoacetate (42 mg, 0.27 mmol) was used instead of 4-fluorobenzyl bromide: 1H NMR (CDCl3) δ 7.43 (m, 1H), 7.26–7.21 (m, 4H), 7.07 (m, 1H), 6.58 (m, 1H), 5.84 (m, 1H), 5.10 (m, 1H), 4.78 (m, 1H), 3.91 (m, 1H), 3.78 (m, 3H), 3.71 (m, 1H), 3.31 (m, 2H), 2.74 (m, 2H), 2.40 (s, 3H), 2.21 (m, 1H), 2.05 (m, 1H), 1.52 (m, 1H), 1.39 (s, 9H), 1.04 (t, 3H, J=7.15 Hz); MS (ESI+) 540.21 (M++H).

Sources & evidence

ORD record: ord-859610acf5a94b9d824b4fd517d3684a
Source dataset: uspto-grants-2006_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07030118B2

Reaction notes

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