tert-butyl (3R)-3-aminopiperidine-1-carboxylate → 4-((R)-9-cyclopentyl-7-fluoro-5-methyl-6-oxo-7-vinyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-((R)-piperidin-3-yl)benzamide

HRID 1880955Notes

Reaction equation

HRID 1880955 reaction equation
[CH:1]1([N:7]2[CH2:13][C@:12]([F:16])([CH:14]=[CH2:15])[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](O)=[O:29])=[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:50][C:45]2[CH:46]=[CH:47][CH:48]=[N:49][C:44]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N1CCC[C@@H](N)C1)(OC(C)(C)C)=O>>[CH:1]1([N:7]2[CH2:13][C@:12]([F:16])([CH:14]=[CH2:15])[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:50][C@@H:45]5[CH2:46][CH2:47][CH2:48][NH:49][CH2:44]5)=[O:29])=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:8]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 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 252533744-((R)-9-cyclopentyl-7-fluoro-5-methyl-6-oxo-7-vinyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-((R)-piperidin-3-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 (R)-1-Boc-3-aminopiperidine. Further, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group was removed using 40% TFA in dichloromethane (6 ml) and purified the product using preparative HPLC and basified using sodium bicarbonate solution to give free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20-1.33 (m, 2 H) 1.30-1.80 (m, 7 H) 1.81-2.02 (m, 4 H) 2.31-2.45 (m, 2 H) 2.81 (d, J=12.63 Hz, 1 H) 2.97 (d, J=8.08 Hz, 1 H) 3.29 (s, 3 H) 3.71-3.90 (m, 3 H) 3.94 (s, 3 H) 4.89 (d, J=8.59 Hz, 1 H) 5.32-5.45 (m, 2 H) 6.01 (ddd, J=17.56, 12.76, 10.86 Hz, 1 H) 7.41-7.53 (m, 2 H) 7.82 (s, 1 H) 8.00 (d, J=7.83 Hz, 1 H) 8.12 (s, 1 H) 8.31 (d, J=8.08 Hz, 1 H). [M+H] calc'd for C28H36FN7O3, 538; found 538.

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
  4. custompurified the product
  5. customto give free base

Sources & evidence

ORD record
ord-5e026a2051154e0fa7eba2ce979388ce
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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