4-Amino-1-Boc-piperidine → 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-(2-(pyrrolidin-1-yl)acetyl)piperidin-4-yl)benzamide

HRID 914065Notes

Reaction equation

HRID 914065 reaction equation
[CH:1]1([N:7]2[CH2:13][C@:12]([F:16])(C=C)[C:11](=[O:17])[N:10]([CH3:18])[C:9]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([OH:30])=O)=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:8]2=3)C[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=N[C:45]2[CH:46]=[CH:47][CH:48]=[N:49][C:44]1=2)=[N+](C)C)C.[F:52][P-](F)(F)(F)(F)F.[C:59]([N:66]1[CH2:71][CH2:70][CH:69]([NH2:72])[CH2:68][CH2:67]1)([O:61]C(C)(C)C)=O>>[CH:1]1([N:7]2[CH2:13][C:12]([F:52])([F:16])[C:11](=[O:17])[N:10]([CH3:18])[C:9]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([NH:72][CH:69]5[CH2:68][CH2:67][N:66]([C:59](=[O:61])[CH2:44][N:49]6[CH2:48][CH2:47][CH2:46][CH2:45]6)[CH2:71][CH2:70]5)=[O:30])=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:8]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 3

HCID 12682914-Amino-1-Boc-piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67117829(R)-4-(9-cyclohexyl-7-fluoro-7-vinyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid

Product 1

HCID 252532194-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-(2-(pyrrolidin-1-yl)acetyl)piperidin-4-yl)benzamide

Procedure

The title compound was synthesized from (R)-4-(9-cyclohexyl-7-fluoro-7-vinyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-Boc-4-aminopiperidine. Further, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group was removed using 40% TFA in dichloromethane (6 ml). The resulting product was further acylated using 2-(pyrrolidin-1-yl)acetyl chloride. The title product using preparative HPLC and neutralized with bicarbonate. 1H NMR (400 MHz, DMF) δ ppm 1.53-2.30 (m, 18H) 2.79-3.01 (m, 2H) 3.21-3.47 (m, 5H) 4.17 (s, 3H) 4.21-4.41 (m, 6H) 4.59 (d, J=12.13 Hz, 1H) 5.00 (t, J=8.34 Hz, 1H) 7.71 (d, J=1.77 Hz, 2H) 8.21 (s, 1H) 8.40 (d, J=7.83 Hz, 1H) 8.50 (s, 2H). [M+H] calc'd for C32H42F2N8O4, 641. found 641.

Workup

  1. customas described in the General procedure for amide bond synthesis
  2. washFurther, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group
  3. customwas removed

Sources & evidence

ORD record
ord-d1f9e83ada15499cb1005a4618d92cfd
Source dataset
uspto-grants-2011_09
Patent number
US08026234B2

Reaction notes

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